Effects of magnesium sulphate and nitric oxide in pulmonary hypertension induced by hypoxia in newborn piglets

AIM: To examine the haemodynamic effects of intravenous magnesium sulphate on an animal model of neonatal pulmonary hypertension induced by hypoxia. METHODS: The cardiac index (Q), pulmonary arterial pressure (PAP), systemic arterial pressure (SAP), and pulmonary (PVRI) and systemic (SVRI) vascular resistance indices were measured in nine newborn piglets (including three controls). Pulmonary hypertension was induced by lowering the FIO2 to 0.12-0.14, after which there was a significant increase in PAP and PVRI (37% and 142%, respectively; p < 0.01) and a significant fall in SAP and Q (30% and 33%, respectively; p < 0.01). RESULTS: Magnesium sulphate was infused intravenously as four doses of 25 mg/kg, 15 minutes apart, which resulted in a significant mean (SD) increase in serum magnesium (0.83 (0.07) mmol/l to 1.82 (0.19) mmol/l; p < 0.01). After the initial dose SAP, SVRI, PAP and PVRI decreased, but not significantly. Each subsequent dose of (50, 75, 100 mg/kg) was accompanied by further significant reductions in these variables from control baseline (p < 0.05). The PVRI:SVRI ratio remained unchanged throughout. Inhaled nitric oxide (NO) 40 ppm was administered after the last dose of magnesium sulphate. The PVRI:SVRI significantly decreased (p < 0.05), indicating that reversible pulmonary hypertension remained after a maximum dose of magnesium sulphate. CONCLUSIONS: Unlike NO, magnesium sulphate is not a selective pulmonary vasodilator and may lead to deleterious effects on systemic pressures in critically ill newborns.     

Comparison of biological activity of high molecular weight and low molecular weight forms of immunoreactive prolactin from human serum in cultured lymphoma NB2 cells

The aim of this study was to determine the cardiac performance of conscious healthy dogs during stimulation with dobutamine. Eight healthy unsedated beagle dogs were used. Cardiac output was measured by the thermodilution technique and blood pressures by extravascular pressure transducers. Dobutamine challenge at a dosage ranging from 27.5 to 50 micrograms kg-1 min-1 induced a significant rise in cardiac power index (CPI), cardiac index (CI), stroke index (SI) and heart rate (HR) and a significant decrease in pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR). The highest CPI was 2.05 times greater than its basal resting value. The CI was primarily responsible for this increase in CPI. The SI and HR contributed approximately 55 per cent and 45 per cent respectively of the maximal increase in CI.     

Hypotension during subarachnoid anaesthesia: haemodynamic effects of colloid and metaraminol

We have studied 45 patients, aged 60-95 yr, receiving subarachnoid block for neck of femur fractures. Patient received either colloid (polygeline, Haemaccel) 8 ml kg-1 (n = 15), metaraminol 5 micrograms kg-1 and 1.7 micrograms kg-1 min-1 (n = 15) or a combination of both treatments to maintain systolic arterial pressure (SAP) between 75 and 100% of baseline. If necessary, additional colloid 2 x 4 ml kg-1 or metaraminol 3 x 2.5 micrograms kg-1 was given. Arterial pressure was measured by automated oscillotonometry, central venous pressure (CVP) by a manometer and cardiac index (CI), stoke index (SI) and heart rate (HR) by transthoracic electrical bioimpedance. Systemic vascular resistance index (SVRI) was derived. Colloid was less effective than metaraminol (P < 0.05). In the colloid group, SAP and SVRI decreased and CVP, CI and SI increased (P < 0.001). In the metaraminol group, initial decreases in SAP, SVRI and CVP were restored after 10-15 min and HR decreased after 12 min (P < 0.001). In the combined group, initial decreases in SAP and SVRI were restored after 4 and 16 min, and CVP, CI, SI and HR increased (P < 0.001). Metaraminol was more effective than colloid because it increased SVRI, whereas colloid increased CVP without significantly increasing CI.     

Haemodynamic changes in neurogenic pulmonary oedema: effect of dobutamine

The haemodynamic and gas exchange abnormalities occurring in neurogenic pulmonary oedema (NPO) were examined retrospectively in 20 patients admitted to the Intensive Therapy Unit (ITU) over a 45-month period (February 1992 to November 1995). In 12 patients, where vasoactive therapy with dobutamine was employed, its effect on haemodynamics was examined. Cardiac index (CI median 2.2 l min-1 m-2) and left ventricular stroke work index (LVSWI 20 g.m.m-2) were markedly depressed, while pulmonary artery wedge pressure (PAWP 17 mmHg), mean pulmonary artery pressure (MPAP 30.5 mmHg), systemic vascular resistance index (SVRI 2852 dyne.s.cm-5.m2) and pulmonary vascular resistance index (PVRI 393 dyne.s.cm-5.m2) were substantially elevated above normal values. Mean arterial pressure (MAP 82.5 mmHg) and heart rate (HR 102 bpm) were within normal limits. The poor oxygenation is indicated by a median PaO2/fiO2 ratio of 18.0 kPa. Patients treated with dobutamine showed significant increases in CI and LVSWI and significant falls in SVRI and PAWP at 2 and 6 h after institution of therapy, and there was a significant rise in PaO2/fiO2 ratio to 27.8 kPa at 6 h. NPO was generally associated with severe depression of myocardial function and elevation of pulmonary vascular pressures. This dysfunction was readily reversed by dobutamine.     

Role of calciotrophic hormones in calcium mobilization of lactation

In two consecutive studies (Study A and Study B), we evaluated the effects of increasing doses of HBOC-201, a bovine hemoglobin-based oxygen carrier, on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery. After the induction of anesthesia and the exchange of 1 L of blood for 1 L of lactated Ringer's solution, 24 patients (12 in each study) were randomly assigned to receive, within 30 min, a predetermined volume of either HBOC-201 or 6% hydroxyethyl starch (Study A 6.9 mL/kg; Study B 9.2 mL/kg). Monitored variables included systemic and pulmonary arterial pressures, arterial and mixed venous blood gases, and calculations of cardiac index (CI), systemic (SVRI) and pulmonary (PVRI) vascular resistance indices, oxygen delivery index (DO2I), oxygen consumption index (VO2I), and oxygen extraction ratio (O2ER). In both studies, the infusion of HBOC-201 was associated with increases in SVRI (Study A 121%; Study B 71%) and PVRI (Study A 70%; Study B 53%) and with a decrease in CI (29% both studies). Hemodilution with HBOC-201 maintained the arterial oxygen content at levels higher than hemodilution with hydroxyethyl starch, but the advantage of a greater oxygen-carrying capacity was offset by the increase in SVRI, with a resulting net decrease in both CI and DO2I (Study A 30%; Study B 28%); VO2I was maintained by increased O2ER. In terms of hemodynamics and oxygen transport, hemodilution with bovine hemoglobin in these doses provided no apparent benefit over hemodilution with hydroxyethyl starch. Implications: Bovine hemoglobin in doses ranging between 55 and 97 g of hemoglobin increased vascular resistance and decreased cardiac output in anesthetized surgical patients. In terms of hemodynamics and oxygen transport, hemodilution with bovine hemoglobin in these doses provided no apparent benefit over hemodilution with hydroxyethyl starch.     

Effects of aging on left ventricle-arterial coupling in man

Twenty-five normotensive men without any cardiac or arterial pathology, aged 22 to 68 years, 12 less than 45 year old, 13 over 45 years, underwent cardiac catheterisation and angiography. The following parameters were calculated: 1) a global index of arterial function (Ea) and its determining factors (Ea = LVESP/SV where LEVSP = left ventricular end systolic pressure and SV = left ventricular stroke volume); Ea = (HR x SVR) + Ea' where HR = heart rate, SVR = total systemic vascular resistance and Ea' = (LVESP - MAP/SV) (MAP = mean arterial pressure); 2) an index of global left ventricular pump function: ELV (ELV = LVESP/LVESV, where LVEDV = left ventricular end systolic volume; 3) an index of LV-arterial coupling: the Ea/ELV ratio. With aging, both Ea (by increase in SVR) and Ea' and ELV increased significantly. Ea/ELV (inverse of the ejection fraction-1) increased with age but ELV less than Ea. Ea/ELV was significantly higher in patients over 45 years of age but the correlation between ejection fraction and age was not statistically significant (p = 0.10). These results suggest that with aging, the improvement in LV pump function approximately corresponds to the degradation in arterial transport function: the left ventricular-arterial coupling as assessed by the Ea/ELV ratio (and therefore the ejection fraction) is maintained in the majority of cases.     

Topical application of synthetic pyrethroids to cattle as a source of persistent environmental contamination

Norepinephrine (NE) is one of the most potent positive inotropic drugs available for the treatment of low-output state following open-heart surgery. However, its inotropic effect is often masked by a significant increase of peripheral vascular resistance due to marked vasoconstriction. The purpose of the present study was to investigate whether the use of nicardipine (Nc) and phentolamine (Ph) in combination with NE could ameliorate the adverse vasoconstrictive action of NE. A low-output-state (LOS) model was produced by global myocardial ischemia due to electrically induced intermittent ventricular fibrillations in open-chest dogs. Twenty-eight dogs were divided into 6 groups according to the drugs infused after producing LOS. In the control group, hemodynamic changes similar to the clinical low-output state were observed, e.g., a decrease in cardiac output (CO) and left ventricular dp/dt, and an increase in the systemic vascular resistance (SVR). The use of NE alone produced marked increases in the systemic arterial pressure (SAP), heart rate, and SVR, with a slight increase in CO. The infusion of Nc alone produced decreases in SVR and SAP with a slight increase in CO. The concomitant infusion of NE and Nc produced increases in SV and CO, and decreases in SAP and SVR. The infusion of Ph alone produced no significant hemodynamic changes. The combined use of NE and Ph produced increases in CO, SAP and heart rate, but not to a significant extent. These results suggest that there are major advantages in the concomitant use of NE and Nc for the control of LOS.     

Cardio-pulmonary function during acute unilateral occlusion of the pulmonary artery in broilers fed diets containing normal or high levels of arginine-HCl

Cardio-pulmonary function was measured in male broilers reared on diets formulated to contain 1.5% arginine (NORMAL group) or 2.5% arginine (ARGININE group). A snare placed around the right pulmonary artery permitted acute shunting of the entire cardiac output (CO) through the left pulmonary artery, resulting in sustained increases in blood flow (BF) through the left lung in both groups. The unilateral increase in BF was accompanied by sustained increases in pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in the NORMAL group. However, following initial transient increases in PAP and PVR in the ARGININE group, subsequent pulmonary vasodilation gradually reduced PVR, and thus PAP, in spite of the ongoing elevation of BF through the left lung. The capacity of the pulmonary vasculature in the ARGININE group to accommodate an increased BF at a normal PAP accounts for the previously reported lower incidence of pulmonary hypertension syndrome (PHS, ascites) in cold-stressed broilers fed supplemental dietary arginine. Hypoxemia and respiratory acidosis ensued rapidly in both groups after tightening the pulmonary artery snare, in spite of a compensatory increase in the respiratory rate. The gradual return of PVR and PAP to presnare levels in the ARGININE group did not eliminate the concurrent ventilation-perfusion mismatch caused by the increased rate of BF through the left lung. Tightening the pulmonary artery snare caused mean systemic arterial pressure (MAP) to drop from control levels of approximately 98 mm Hg to sustained hypotensive levels of approximately 65 mm Hg in both groups. This systemic hypotension was caused by decreases in CO and total peripheral resistance (TPR). The reduction in CO were caused by reduction in stroke volume (SV) rather than heart rate (HR), suggesting that acutely tightening the pulmonary artery snare increased PVR sufficiently to impede left ventricular filling. Accordingly, the maximum increment in PAP attainable by the right ventricle during acute increases in PVR apparently was inadequate to propel the entire CO through the pulmonary vasculature, setting the stage for the congestive right-sided pooling of blood routinely associated with PHS in broilers.     

Anesthetic management of a patient with hypertrophic cardiomyopathy using propofol, fentanyl and ketamine

A 59-year-old male with hypertrophic cardiomyopathy was scheduled for resection of a maxillary cyst. Metoprolol was discontinued the day before surgery. Thirty min before anesthesia, meperidine 35 mg was administered intramuscularly. After intravenous administration of midazolam 3 mg, a pulmonary catheter was inserted for monitoring hemodynamic parameters. Anesthesia was induced with propofol 75 mg, fentanyl 0.15 mg and ketamine 75 mg. Anesthesia was maintained with continuous infusion of propofol 5 mg.kg-1.h-1 and ketamine 1 mg.kg-1.h-1. Moreover, fentanyl was added as necessary during surgery. Blood pressure (BP), pulmonary arterial pressure (PA), systemic vascular resistance index (SVRI) and pulmonary vascular resistance index (PVRI) were measured using a pulmonary catheter during anesthesia. Since BP decreased after intubation, dopamine 3 micrograms.kg-1.min-1 was administered for 20 min. The hemodynamic state was stable during surgery. However, BP, PA, SVRI and PVRI increased temporally at extubation. His postoperative course was uneventful. In conclusion, total intravenous anesthesia with propofol, fentanyl and ketamine may be useful for anesthetic management of a patient with hypertrophic cardiomyopathy.     

Pulmonary hypertension after transjugular intrahepatic portosystemic shunt: effects on right ventricular function

The short- and mid-term hemodynamic effects of transjugular intrahepatic portosystemic shunt (TIPS) were studied in 16 sedated cirrhotic patients. Indications included relapsing variceal bleeding (n = 10) and refractory ascites (n = 6). The decrease of porto-atrial pressure gradient (from 20.4 +/- 4.2 mm Hg to 10.1 +/- 2.4 mmHg; P < .05) was associated with an increase of mean pulmonary artery pressure (MPAP) (from 12.3 +/- 3.0 mm Hg to 20.3 +/- 5.3 mm Hg; P < .05) and of right atrial pressure (RAP) from 3.4 +/- 2.6 mm Hg to 8.3 +/- 3.7 mm Hg; P < .05), whereas right ventricular end-diastolic volume (RVEDVI) remained unchanged. The significant increase of cardiac index (CI) (from 4.5 +/- 1.2 L/min/m2 to 5.0 +/- 1.1 L/min/m2; P < .05) was essentially attributable to an increase of heart rate (HR) (from 81 +/- 11 to 88 +/- 10 beats/min; P < .05). Systemic vascular resistance (SVR) decreased (from 812 +/- 281 to 666 +/- 191 dynes/sec/cm5; P < .05), whereas pulmonary vascular resistance (PVR) increased (from 60.6 +/- 29.6 to 82.0 +/- 34.6 dynes/sec/cm5; P < .05). After transient shunt occlusion with a balloon catheter, all of the hemodynamic parameters returned to baseline values, except pulmonary artery pressure, which also decreased but remained significantly increased. One month after TIPS, pulmonary pressure remained elevated, and CI further increased. It is concluded that increased PVR is the major hemodynamic alteration occurring after TIPS placement. It correlates with the decrease of porto-atrial gradient and is probably mediated by both mechanical and neurohumoral factors.     

Cardiovascular responses at the onset of static exercise in patients with dual-chamber pacemakers

Cardiac output (CO) responses to exercise can be altered by ventricular pacing in pacemaker-dependent patients. The relative contributions of CO and peripheral vascular resistance (PVR) toward the initial increase in blood pressure with the initiation of static exercise were investigated in eight otherwise healthy pacemaker-dependent subjects [age 24 +/- 2 yr (range 17-37 yr)]. Beat-by-beat measures of heart rate (HR; electrocardiography), mean arterial pressure (MAP), and CO derived from stroke volume (SV) (CO = HR.SV; 2-D echocardiography) were determined during the first 20 s of a one-legged static knee extension performed at 20% maximal voluntary effort by using three pacing modalities: dual pacing and sensing mode (DDD, i.e., normal physiological HR response), fixed at resting HR (DOO-R), and fixed at peak exercise HR (DOO-E), as previously achieved during 5 min of sustained contraction in the DDD mode. There were no differences in MAP, CO, or PVR (PVR = MAP/CO) between modes at rest (P > 0.05). With DOO-E pacing, SV was lower at rest compared with the other modes and increased with exercise (P < 0.05). Although there were no significant increase in MAP or CO during DOO-R pacing, both variables were elevated by leg contraction during DDD and DOO-E pacing (P < 0.05), with no significant change in PVR. Additionally, the CO and MAP increases were significantly greater with DOO-E pacing (P < 0.05). Thus the magnitude of the initial increase in arterial pressure at the onset of mild one-legged static exercise was dictated by the changes in CO as PVR remained unchanged.     

Does the choice of antihypertensive therapy influence haemodynamic responses to induction, laryngoscopy and intubation?

We have measured haemodynamic responses to induction of anaesthesia, laryngoscopy and intubation in 103 mild-moderate hypertensive patients (83 patients (diastolic pressures < or = 110 mm Hg) currently receiving one of four monotherapies (ACE inhibitors, group A; beta adrenoceptor blocking drugs, group B; calcium channel antagonists, group C; diuretics, group D) and 24 were untreated hypertensive patients). Anaesthesia was induced with fentanyl 1.5-2.0 micrograms kg-1 and thiopentone 3-5 mg kg-1. Tracheal intubation was facilitated by vecuronium 0.1 mg kg-1 and anaesthesia maintained with enflurane and nitrous oxide in oxygen. Systolic and diastolic pressures (SAP, DAP) were measured at 1-min intervals by a non-invasive oscillometric method and cardiac output (CO) and stroke volume (SV) by thoracic bioimpedance. Induction of anaesthesia was associated with a decrease in SAP, DAP and CO in groups A-D (P < 0.05). Heart rate (HR) decreased in groups A and D (P < 0.01) and systemic vascular resistance (SVR) decreased in groups A and B (P < 0.05). SAP and HR increased in all groups after laryngoscopy and intubation (P < 0.01) as did SVR in groups A, B and D (P < 0.02). CO was unaltered. Similar changes occurred in the untreated hypertensive patients, although nine of 24 patients exhibited HR > or = 100 beat min-1 after laryngoscopy and intubation. Comparison of the changes in SAP, DAP, CO and SVR with time showed no differences in the five treatment groups; changes in HR were significantly less in group B compared with the other groups (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effect of inhaled nitric oxide in dilated cardiomyopathy patients on LVAD support

Recently it has been shown that inhaled nitric oxide (NO), which has been proven to contribute to improvement in critical pulmonary hypertension, may provide a favorable effect early after left ventricular assist device (LVAD) support. To improve right ventricular function, inhalation of NO was added to treatment with conventional catecholamines for four consecutive dilated cardiomyopathy (DCM) patients following institution of LVAD. In two patients 1 hr after inhalation of NO, central venous pressure (CVP), mean pulmonary arterial pressure (PAm), and pulmonary vascular resistance (PVR) were improved. These results led to better LVAD output and resulted in an adequate cardiac index. On the other hand, a right VAD (RVAD) was implemented in one patient whose high CVP, PAm, and PVR continued; he was weaned after 8 days of RVAD support. Another patient who had a high CVP but normal PAm and PVR before and after inhalation of NO had no improvement in his hemodynamic state. These data suggest that inhaled NO may improve systemic circulation by reducing right ventricular afterload and may become a promising and convenient therapy before placing RVAD in DCM patients under LVAD support. RVAD should be conducted in patients with right ventricular failure or when pulmonary hypertension is associated with impaired right ventricular reserve, even after inhalation of NO.     

Acute effects of transjugular intrahepatic portosystemic stent-shunt (TIPSS) procedure on renal blood flow and cardiopulmonary hemodynamics in cirrhosis

OBJECTIVE: An acute increase in portal pressure is associated with an immediate reduction in renal blood flow. It has been suggested that this supports the presence of an hepatorenal reflex. In this study, we used TIPSS placement as a model to investigate the effect of an acute reduction in portal pressure on renal blood flow and cardiopulmonary hemodynamic parameters. METHODS: Eleven cirrhotic patients were studied during elective TIPSS placement for variceal hemorrhage (n = 9) or refractory ascites (n = 2). Unilateral renal blood flow (RBF) was measured before and at 5, 15, 30, 45, and 60 min after shunt insertion. Heart rate (HR), mean arterial pressure (MAP), right atrial pressure (RAP), mean pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and systemic vascular resistance (SVR) were also measured before and 30 min after TIPSS placement. RESULTS: Despite significant increases in CO (p = 0.001), RAP (p < 0.001), PAP (p < 0.001), and PCWP (p = 0.001), and a fall in SVR (p = 0.003), no change was observed in RBF, HR, or MAP after TIPSS placement. The fall in the portoatrial pressure gradient correlated only with the rise in CO (p < 0.05) and the drop in SVR (p < 0.05). CONCLUSION: Despite the fall in portal pressure and the systemic hemodynamic changes caused by TIPSS placement, there is no immediate effect on RBF. Any improvement in renal function after TIPSS procedure does not appear to be due to an acute increase in RBF.     

Molecular genetics of asymmetric cleavage in the early Caenorhabditis elegans embryo

BACKGROUND: Pharmacological control of blood pressure is usually indicated during aortic cross-clamping (AXC). The aim of this study was to analyze the modulation by isoflurane (ISO), sodium nitroprusside (SNP) and milrinone (MIL) of the systemic circulatory responses to a standardized infra-renal AXC. METHODS: Chloralose-anaesthetized pigs were exposed to AXC at control (no vasoactive drugs) and during the administration of each of the drugs. RESULTS: During control, AXC increased mean arterial pressure (MAP, 17 +/- 4%) and systemic vascular resistance (SVR, 27 +/- 7%), but induced no significant changes in cardiac output (CO), heart rate (HR), pulmonary arterial pressures, pulmonary vascular resistance or central venous pressure. Low-dose ISO (0.7%) and investigated doses of SNP and MIL did not significantly alter this response. High-dose ISO (1.4%, attenuated the AXC-induced increase in SVR, but not in MAP. All drugs decreased non-clamp MAP levels. Therefore, with low-dose ISO and with SNP or MIL, peak MAP during AXC was not significantly different from control non-clamp levels (i.e. prior to pharmacological or surgical interventions). High-dose ISO was associated with a MAP during AXC that was below control non-clamp levels. CONCLUSIONS: The objective that during AXC MAP should not exceed control non-clamp levels was achieveable by ISO, SNP or MIL. The modulating actions of the drugs on MAP during AXC were exerted mainly through reductions in non-clamp levels. This systemic hypotension was associated with decreased CO and SVR during ISO, and with decreased SVR and increased HR during SNP and MIL. Attenuation of the AXC-induced increase in SVR was produced only by 1.4% ISO.     

Differential role of endothelium-derived nitric oxide in the modulation of the systemic and pulmonary circulation in lambs

We have studied the differential role of endothelium-derived nitric oxide (EDNO) in the regulation of the systemic and pulmonary circulations of the lamb. Hemodynamic effects of NG-nitro-L-arginine methyl ester (L-NAME, 1 mg/kg i.v.), an inhibitor of NO synthesis, were determined in juvenile (6 +/- 1 weeks old) lambs, under conditions of basal and elevated vasomotor tone. Under basal conditions, L-NAME raised both systemic (SVR) and pulmonary vascular resistances (PVR) by 20-30% (increasing SVR from 0.318 +/- 0.013 to 0.385 +/- 0.015 mm Hg.min.ml-1.kg and PVR from 0.050 +/- 0.003 to 0.067 +/- 0.010 mm Hg.min.ml-1.kg). When tone was elevated in the pulmonary circulation with hypoxia (PVR was elevated by 60%, from 0.059 +/- 0.010 to 0.094 +/- 0.019 mm Hg.min.ml-1.kg), L-NAME treatment resulted in an augmented increase in PVR (PVR increased by greater than 50% to 0.140 +/- 0.024 mm Hg.min.ml-1.kg). However, when tone was elevated to a comparable degree in the systemic circulation with angiotensin infusion (SVR was elevated by 60%, from 0.432 +/- 0.065 to 0.065 to 0.634 +/- 0.113 mm Hg.min.ml-1.kg), the response to L-NAME was not augmented. Our data suggest that the role of EDNO in the modulation of the pulmonary circulation is dependent on the level of vasomotor tone, whereas its role in the systemic circulation is small and is independent of the level of vasomotor tone.     

Peripheral vascular versus direct cardiac effects of calcium

Peripheral vascular and direct cardiac effects of calcium chloride were determined in a new animal model, the unanesthetized calf, before and after replacement of its natural heart (NH) with a pneumatically driven artificial heart (AH). Calcium (5 and 10 mg/kg) significantly increased cardiac output (Qt) and reduced systemic vascular resistance (SVR) before and after AH implantation. Increases in Qt in AH calves and reductions in SVR in both NH and AH calves were, however, transient, being present 5 minutes but not 15 minutes after both doses of calcium. Increases in Qt and reductions in SVR were significantly (P less than .05) greater after 10 mg/kg than after 5 mg/kg calcium in NH and AH calves. Both doses of calcium produced greater (P less than .05) increases of Qt in NH than in AH animals but similar reductions in SVR. Pulmonary vascular resitance, heart rate and pulmonary arterial and right atrial pressures were not significantly altered by either dose of calcium in NH or AH calves. Mean aortic pressure was influenced by 10 mg/kg calcium only, being transiently reduced in AH calves and increased in NH animals. Pulmonary shunt (QS/Qt) was increased by both doses of calcium in NH calves but only by 10 mg/kg in AH animals. Correlations of mean change in QS/Qt with mean change in Qt were high both before (r=.99) and after (r=.97) AH implantation. These data demonstrate that calcium significantly reduces SVR in a dose-related manner as well as exerting a positive inotropic effect on the myocardium.     

Biphasic graft preservation for lung transplantation

The standard, most widely applied way of preserving a lung for transplantation is infusion through the pulmonary artery (PA) of a pulmonaryplegic solution. In this prospective study, we analyzed the initial function of the pulmonary and cardiac graft after biphasic infusion of a solution introduced retrograde through the left auricle and antegrade through the PA. Twenty-six heart and lung grafts (9 unilateral and 17 bilateral) were preserved by cardioplegia and pulmonaryplegia (biphasic) between January 1996 and March 1997. Indicators of graft viability recorded were the ratio of arterial oxygen pressure (PaO2) to inspired fraction (FiO2), mean systemic pressure (MSP), mean pulmonary artery pressure (MPAP) cardiac output, pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR). The variables were recorded upon arrival of the grafts in the intensive care unit and in the first 24 h. Morbidity and mortality after heart transplants were recorded throughout a follow-up period of one month. After transplantation, most patients had a oxygenation coefficient (PaO2/FiO2) greater than 252 mmHg in the first 48 h. Hemodynamic parameters were also kept within normal ranges immediately after surgery and 24 h later. Mean ischemic time was 245 min for unilateral transplants, 215 for the first lung in double lung transplants, and 300 min for the second lung. In the early postoperative period, 3 patients suffered lung graft dysfunction, which was treated satisfactorily with nitric oxide (NO). No heart transplant patient suffered primary heart failure or left ventricular dilatation. We conclude that biphasic pulmonary preservation achieves satisfactory initial functional viability of the graft. Heart grafts removed simultaneously functioned successfully in the transplanted patient without additional pharmacological or mechanical support.     

Mechanisms for increasing stroke volume during static exercise with fixed heart rate in humans

Ten patients with preserved inotropic function having a dual-chamber (right atrium and right ventricle) pacemaker placed for complete heart block were studied. They performed static one-legged knee extension at 20% of their maximal voluntary contraction for 5 min during three conditions: 1) atrioventricular sensing and pacing mode [normal increase in heart rate (HR; DDD)], 2) HR fixed at the resting value (DOO-Rest; 73 +/- 3 beats/min), and 3) HR fixed at peak exercise rate (DOO-Ex; 107 +/- 4 beats/min). During control exercise (DDD mode), mean arterial pressure (MAP) increased by 25 mmHg with no change in stroke volume (SV) or systemic vascular resistance. During DOO-Rest and DOO-Ex, MAP increased (+25 and +29 mmHg, respectively) because of a SV-dependent increase in cardiac output (+1.3 and +1.8 l/min, respectively). The increase in SV during DOO-Rest utilized a combination of increased contractility and the Frank-Starling mechanism (end-diastolic volume 118-136 ml). However, during DOO-Ex, a greater left ventricular contractility (end-systolic volume 55-38 ml) mediated the increase in SV.     

Induction of ventricular collapse by an axial flow blood pump

An important consideration for clinical application of rotary blood pump based ventricular assist is the avoidance of ventricular collapse due to excessive operating speed. Because healthy animals do not typically demonstrate this phenomenon, it is difficult to evaluate control algorithms for avoiding suction in vivo. An acute hemodynamic study was thus conducted to determine the conditions under which suction could be induced. A 70 kg calf was implanted with an axial flow assist device (Nimbus/UoP IVAS; Nimbus Inc., Rancho Cordova, CA) cannulated from the left ventricular apex to ascending aorta. On initiation of pump operation, several vasoactive interventions were performed to alter preload, afterload, and contractility of the left ventricle. Initially, dobutamine increased contractility and heart rate ([HR] = 139; baseline = 70), but ventricular collapse was not achievable, even at the maximal pump speed of 15,000 rpm. Norepinephrine decreased HR (HR = 60), increased contractility, and increased systemic vascular resistance ([SVR] = 24; baseline = 15), resulting in ventricular collapse at a pump speed of 14,000 rpm. Isoproterenol (beta agonist) increased HR (HR = 103) and decreased SVR (SVR = 12), but ventricular collapse was not achieved. Inferior vena cava occlusion reduced preload, and ventricular collapse was achieved at speeds as low as 11,000 rpm. Esmolol (beta1 antagonist) decreased HR (HR = 55) and contractility, and ventricular collapse was achieved at 11,500 rpm. Episodes of ventricular collapse were characterized initially by the pump output exceeding the venous return and the aortic valve remaining closed throughout the cardiac cycle. If continued, the mitral valve would remain open throughout the cardiac cycle. Using these unique states of the mitral and aortic valves, the onset of ventricular collapse could reliably be identified. It is hoped that the ability to detect the onset of ventricular collapse, rather than the event itself, will assist in the development and the evaluation of control algorithms for rotary ventricular assist devices.