Effect of acute alterations in afterload on left ventricular function in patients with combined coronary artery and peripheral vascular disease

The GTP analog guanylylmethylene diphosphonate (GppCH2p) strongly inhibited polyuridylic acid-directed polypeptide synthesis in a cell-free translation system prepared from Agrobacterium tumefaciens. Fusidic acid increased even further the inhibitory action. The pre-translocational ribosomal complexes formed with the GppCH2p and the elongation factor G protected the ribosome against the depurinating action of crotin 2 assayed as the acid-dependent release of the RNA fragment whose terminal sequence is 5'-GAGGACCGGGAUGGAC-3'. The results allowed to conclude that the interaction of both crotin 2 and the elongation factor G with the A. tumefaciens ribosomes in the pre-translocational state must take place at overlapping, either sterically or allosterically, ribosomal sites which are equally accessible to the RIP.     

Differential alterations in left and right ventricular G-proteins in congestive heart failure due to myocardial infarction

In order to examine the status of G-proteins in congestive heart failure due to myocardial infarction, the left coronary artery in rats was ligated and animals assessed after 4, 8 and 16 weeks. Sham-operated control and experimental animals were used for the preparation of membranes from the viable (uninfarcted) left and right ventricles. Adenylyl cyclase activities in the presence of pertussis toxin and cholera toxin were increased and decreased in left ventricles from all groups, respectively. On the other hand, adenylyl cyclase activities in 8 and 16-week experimental right ventricles were unaltered in the presence of pertussis toxin and increased in the presence of cholera toxin. Depression of adenylyl cyclase activities in left ventricles from all groups as well as in the right ventricle at 4 weeks were not evident when enzyme activity was determined in the pertussis toxin-treated membranes in the absence or presence of Gpp(NH)p. Cholera toxin-catalyzed ADP ribosylation was decreased in left ventricles from all infarcted groups and increased in the right ventricles at 8 and 16 weeks whereas the pertussis toxin-catalyzed ADP ribosylation was increased in all experimental tissues except in the right ventricles at 8 and 16 weeks. G(s alpha)-protein content was decreased in the left ventricle at 16 weeks and increased in the right ventricles at 8 and 16 weeks of myocardial infarction. On the other hand, G(i alpha)-protein content was increased in left ventricles from all infarcted groups and the 4-week right ventricle but was unaltered in 8 and 16-week right ventricles. An increase in mRNA abundance for G(i alpha)-protein was seen in both left and right ventricles following myocardial infarction. A significant increase in mRNA level for G(s alpha)-protein was observed in all left ventricles and 8-week right ventricle following the coronary occlusion. These results suggest that changes in Gs- and Gi-proteins in the failing heart due to myocardial infarction are chamber-specific and are dependent upon the stage of congestive heart failure.     

Doppler echocardiographic assessment of left atrial and left ventricular function during right bundle branch block]

Electrocardiographic, echocardiographic and Doppler echocardiographic studies were performed in 44 patients with coronary heart disease and complete right bundle branch block. The patients were found to have an impaired phase pattern of left ventricular systole and diastole as more prolonged length of its isometric relaxation and contraction, lower economic feasibility and efficiency of its contraction, moderate dilation and hypertrophy. Hemodynamic abnormalities in the left heart in these patients are closely correlate with the changes in the phase pattern of right ventricular systole and they turn out to be so greater as the degree of its hypertrophy is. In complete right bundle branch block, left ventricular pump dysfunction leads to decreased cardiac output and cardiac index, increased total peripheral vascular resistance, thus predisposing to impaired greater circulation.     

Effects of intracoronary caffeine on left ventricular mechanoenergetics in Ca2+ overload failing rat hearts

Perioperative cardiac events are the largest cause of morbidity and mortality for patients undergoing elective surgery. As a result, numerous recent studies have focused on attempts to identify patients at increased risk for perioperative events. These have delineated testing modalities capable of identifying high-risk patients, and clinical markers which further stratify patients facing elective surgery into high-, medium-, and low-risk subgroups. In this article, the authors review the evidence supporting the use of clinical markers of risk to evaluate patients before elective surgery. The role of preoperative clinical assessment in identifying patients most likely to benefit from further testing or intervention, (ie, those at significant risk for short- and long-term cardiac events) is stressed. Assessment and intervention for risk factors of long-term cardiac disease is also stressed, as the preoperative evaluation represents an opportunity for improvement in the short- and long-term cardiac risk profile. Finally, the algorithm for preoperative cardiovascular evaluation published jointly by the ACC/AHA joint taskforce on practice guidelines is reviewed. This algorithm is a synthesis of the current literature, into a cost effective and efficient approach to patient evaluation.     

Dexmedetomidine produces similar alterations in the determinants of left ventricular afterload in conscious dogs before and after the development of pacing-induced cardiomyopathy

BACKGROUND: The authors tested the hypothesis that intravenous dexmedetomidine produces alterations in left ventricular (LV) afterload that are deleterious to cardiac performance in conscious dogs with pacing-induced cardiomyopathy. METHODS: Dogs (n = 8) were fitted with instruments for long-term measurement of LV and aortic blood pressure, aortic blood flow, and subendocardial segment length and received dexmedetomidine (1.25, 2.5, and 5 microg/kg) in a cumulative manner before and after 19+/-3 (mean +/- SEM) days of rapid LV pacing. LV afterload was measured with aortic input impedance [Zin(omega)] and quantified with a three-element Windkessel model. Hemodynamics and Zin(omega)) were assessed under control conditions and 5 and 60 min after administration of each dose. RESULTS: Dexmedetomidine caused early and late decreases in heart rate, the maximum rate of increase of LV pressure, mean aortic blood flow, and stroke volume in dogs before and after pacing. Dexmedetomidine caused similar early increases in total arterial resistance and decreases in total arterial compliance in dogs before and after pacing. Early dexmedetomidine-induced increases in resistance and decreases in compliance caused similar reductions in mean aortic blood flow in cardiomyopathic compared with healthy dogs. Resistance and compliance returned to control values, and characteristic aortic impedance decreased late after dexmedetomidine in healthy dogs. In contrast, resistance remained elevated late after dexmedetomidine in dogs with dilated cardiomyopathy. CONCLUSIONS: Dexmedetomidine causes similar alterations in hemodynamics and LV afterload in conscious dogs with and without pacing-induced cardiomyopathy.     

Comparison of left and right ventricular function in acute myocardial infarction

Pulmonary arterial end-diastolic and mean right atrial pressures were compared in 25 patients with acute myocardial infarction and in one patient with unstable angina. No consistent relationship was observed between these pressures. Simultaneous ventricular function curves relating the stroke work of each ventricle to its respective filling pressure were constructed on 34 occasions, dextran infusion or diuresis being used to alter the filling pressure. The curves from each ventricle were described mathematically by a quadratic (parabolic) function as well as by a straight line function and then compared by canonical correlation analysis. Alterations in the left ventricular function curves occurred with and without depression or right ventricular function curves. These hemodynamic measurements demonstrate that acute myocardial infarction can alter the relationship between left and right ventricular function.     

Relationships between myocardial bioenergetic and left ventricular function in hearts with volume-overload hypertrophy

BACKGROUND: Left ventricular (LV) hypertrophy secondary to volume overload can result in alterations in myocardial bioenergetics and LV dysfunction. This study examined whether bioenergetic abnormalities contribute to the pump dysfunction. METHODS AND RESULTS: Severe mitral regurgitation (MR) was produced in 10 dogs by disruption of the chordal apparatus. Hemodynamics and ventricular function were examined 11.7 months later under baseline conditions and during treadmill exercise. Myocardial high-energy phosphates were measured by using magnetic resonance spectroscopy at rest, during coronary vasodilation with adenosine, and during oxidative stress induced by rapid pacing and dobutamine. Chronic MR caused a 30% increase in LV mass and a 65% increase in LV volume. In MR animals, the hemodynamic and LV function were normal at rest, but abnormalities developed during beta-blockade and exercise. Myocardial creatine phosphate-to-ATP ratios were significantly lower in each layer across the LV wall in MR hearts than normal hearts. Myocardial blood flow and coronary reserve were normal in MR hearts. Moreover, hyperperfusion did not correct the abnormal bioenergetics. Despite altered bioenergetics at rest, the MR hearts tolerated rapid pacing and dobutamine infusion well. CONCLUSIONS: In volume-overloaded LV hypertrophied hearts, alterations in myocardial high-energy phosphate levels do not induce abnormal mechanical performance at rest but may be related to a decreased contractile reserve during exercise.     

Dispersion of ventricular repolarization in left ventricular hypertrophy: influence of afterload and dofetilide

INTRODUCTION: Increased dispersion of ventricular repolarization is observed in cardiac hypertrophy and is associated with sudden cardiac death. At present, there is little information about the effects of cardiac hemodynamics and antiarrhythmic drugs on dispersion of repolarization in disease states. We compared the effects of increasing afterload and the Class III antiarrhythmic drug, dofetilide, on dispersion of ventricular repolarization in hypertrophied rabbit hearts to normal rabbit hearts. METHODS AND RESULTS: Cardiac hypertrophy was induced in rabbits by abdominal aortic banding. Isolated hearts were studied 49+/-4 days postsurgery in the working heart mode using a blood-buffer perfusate. The action potential duration (APD) was measured from eight sites on the epicardium of the heart at low (50+/-7 mmHg) afterload and high afterload (97+/-12 mmHg) at baseline and during dofetilide perfusion. APD dispersion, determined as the difference between the maximal and minimal APD, was greater in hypertrophied hearts (42+/-8 msec) compared with control hearts (26+/-8 msec, P < 0.05) at baseline and low afterload. Increasing afterload caused a decrease in APD dispersion in hypertrophied hearts (P < 0.05) but not in control hearts, and APD dispersion was similar in hypertrophied hearts (31+/-9 msec) compared with control hearts (30+/-9 msec, P = NS). During dofetilide perfusion, APD dispersion remained greater in hypertrophied hearts (60+/-39 msec) compared with control hearts (30+/-13 msec, P < 0.05) at low afterload but not high afterload. Increasing afterload caused shortening of the APD in most regions of the control hearts, whereas APD did not shorten significantly in hypertrophied hearts at baseline and tended to increase during dofetilide perfusion. During dofetilide perfusion, the maximal change in APD recorded from the posterior wall of the left ventricle following an increase in afterload was -18+/-21 msec in control hearts and 7+/-21 ms in hypertrophied hearts (P < 0.05). CONCLUSION: Epicardial APD dispersion decreases in hypertrophied hearts following an increase in afterload, and this response is mediated in part by the absence of afterload-induced shortening of the APD. This effect may be due in part to altered responses of the delayed rectifying current to cardiac loading conditions in the setting of cardiac hypertrophy.     

Influence of right ventricular stimulation site on left ventricular function in atrial synchronous ventricular pacing

Septic shock is a dangerous condition with high mortality rates. In sepsis, the inducible form of nitric oxide (NO) synthase is induced, releasing high amounts of NO. Glucocorticoids have potent anti-inflammatory properties and are very effective in inhibiting the induction of this enzyme if administered before the shock onset. It is known that glucocorticoid receptor (GR) has critical cysteine residues for steroid binding in its hormone-binding and DNA-binding domains. It has also been reported that NO reacts with ---SH groups, forming S-nitrosothiols. Therefore, we examined the potential effect of NO on the ligand-binding ability of GR. NO donors (S-nitroso-acetyl-DL-penicillamine, S-nitroso-DL-penicillamine, or S-nitroso-glutathione) decreased, in a time- and dose-dependent manner, the binding of [3H]triamcinolone to immunoprecipitated GR from mouse L929 fibroblasts. The nonnitrosylated parent molecules, N-acetyl-DL-penicillamine, and reduced gluthatione were without effect. Scatchard plots revealed that the number of ligand binding sites and Kd were reduced (50%) by NO donors. Western blot analysis ruled out the possibility that dissociation of GR/heat shock protein 90 heterocomplex or decrease in GR protein would account for the inhibitory effect of NO. Decreased ligand binding to GR was found when NO donors were incubated with intact fibroblasts. Incubation with NO donors also decreased the steroid-induced reduction in [3H]uridine incorporation into RNA. All of these NO effects were inhibited by the thiol-protecting agent dithiothreitol. Therefore, S-nitrosylation of critical ---SH groups in GR by NO with consequent decreases in binding and affinity may be the mechanisms which explain the failure of glucocorticoids to exert their anti-inflammatory effects in septic shock.     

Acute alterations in systolic ventricular interdependence-mechanical dependence of right ventricle on left ventricle following acute alteration of right ventricular free wall

The purpose of the study was to examine whether systolic ventricular interdependence can be acutely altered by changes in the mechanical properties of the ventricular wall. In eight acute canine studies, we released an aortic constriction during diastole. We measured right ventricular (RV) pressure changes (dPr) caused by sudden changes in left ventricular (LV) pressure (dPl). Measurements were obtained during control, 10 min after right coronary artery occlusion, and then 15 min after injecting glutaraldehyde into the RV free wall. By superimposing the pressure tracings of the beats immediately before and after the aortic release, the instantaneous pressure difference ratio (dPr/dPl) was calculated during systole. Maximal value of the pressure difference ratio decreased from control 0.11 +/- 0.04 to ischemia 0.08 +/- 0.03; (p < 0.05) and increased with glutaraldehyde 0.15 +/- 0.06; (p < 0.05). Thus, acute ischemia in RV free wall decreased the magnitude of systolic ventricular interdependence from LV to RV, while glutaraldehyde, which stiffens the RV free wall, increased the magnitude.     

Differential expression of heat shock proteins in normal and failing human hearts

OBJECTIVE: To predict spinal cord ischemia after endovascular stent graft repair of descending thoracic aortic aneurysms, temporary interruption of the intercostal arteries (including the aneurysm) was performed by placement of a novel retrievable stent graft (Retriever) in the aorta under evoked spinal cord potential monitoring. METHODS: From February 1995 to October 1997, endovascular stent graft repair of descending thoracic aortic aneurysms was performed in 49 patients after informed consent was obtained. In 16 patients with aneurysms located in the middle and distal segment of the descending aorta, the Retriever was placed temporarily before stent graft deployment. The Retriever consisted of two units of self-expanding zigzag stents connected in tandem with stainless steel struts. Each strut was collected in a bundle fixed to a pushing rod, and the stent framework was lined with an expanded polytetrafluoroethylene sheet. The Retriever was delivered beyond the aneurysm through a sheath and was retracted into the sheath 20 minutes later. A stent graft for permanent use was deployed in patients whose predeployment test results with the Retriever were favorable. Evoked spinal cord potential was monitored throughout placement of the Retriever and stent grafting until the next day. RESULTS: The Retriever was placed in 17 aneurysms in 16 patients. There were no changes in amplitude or latency of evoked spinal cord potential records obtained before or during Retriever placement. After withdrawal of the Retriever, all aneurysms were excluded from circulation immediately after permanent stent grafting. There were no changes in evoked spinal cord potential, nor were neurologic deficits seen after stent graft deployment in any patient. CONCLUSIONS: These results suggest that predeployment testing with the Retriever under evoked spinal cord potential monitoring is promising as a predictor of spinal cord ischemia in candidates for stent graft repair of thoracic aortic aneurysms.     

Effects of continuous positive airway pressure on obstructive sleep apnea and left ventricular afterload in patients with heart failure

BACKGROUND: The objectives of this study were to determine the effects of continuous positive airway pressure (CPAP) on blood pressure (BP) and systolic left ventricular transmural pressure (LVPtm) during sleep in congestive heart failure (CHF) patients with obstructive sleep apnea (OSA). In CHF patients with OSA, chronic nightly CPAP treatment abolishes OSA and improves left ventricular (LV) ejection fraction. We hypothesized that one mechanism whereby CPAP improves cardiac function in CHF patients with OSA is by lowering LV afterload during sleep. METHODS AND RESULTS: Eight pharmacologically treated CHF patients with OSA were studied during overnight polysomnography. BP and esophageal pressure (Pes) (ie, intrathoracic pressure) were recorded before the onset of sleep and during stage 2 non-rapid eye movement sleep before, during, and after CPAP application. OSA was associated with an increase in systolic BP (from 120.4+/-7.8 to 131.8+/-10.6 mm Hg, P<0.05) and systolic LVPtm (from 124.4+/-7.7 to 137.2+/-10.8 mm Hg, P<0.05) from wakefulness to stage 2 sleep. CPAP alleviated OSA, improved oxyhemoglobin saturation, and reduced systolic BP in stage 2 sleep to 115.4+/-8.5 mm Hg (P<0.01), systolic LVPtm to 117.4+/-8.5 mm Hg (P<0.01), heart rate, Pes amplitude, and respiratory rate. CONCLUSIONS: In CHF patients with OSA, LV afterload increases from wakefulness to stage 2 sleep. By alleviating OSA, CPAP reduces LV afterload and heart rate, unloads inspiratory muscles, and improves arterial oxygenation during stage 2 sleep. CPAP is a nonpharmacological means of further reducing afterload and heart rate during sleep in pharmacologically treated CHF patients with OSA.     

The heart rate performance curve and left ventricular function during exercise in patients after myocardial infarction

PURPOSE: The aim of the study was to investigate the heart rate turn point (HRTP) in the time course of the heart rate performance curve (HRPC) in patients after myocardial infarction, and the relationship between the HRTP, the left ventricular function, and the second lactate turn point (LTP2). METHODS: We studied the degree and the direction of the HRPC and the left ventricular ejection fraction (LVEF) in 49 male patients 57 +/- 8 d after their first posterior wall infarction (MI). An incremental cycle ergometer test was performed and three phases of energy supply were defined (I: aerobic; II: aerobic-anaerobic transition; III: anaerobic) via blood lactate LA concentration. HRTP and LVEF-turn points (LVEFTP) were assessed by linear turn point analysis. The degree and direction of the deflection of HRPC were described as factor k (k > 0.1: downward deflection; -0.1 < k < 0.1: linear time curse; k < -0.1: upward deflection). The LVEF was determined by RNA. The difference between Pmax and LTP2 was calculated for LVEF (delta LVEF). RESULTS: An HRTP could be found in 44 and a LVEFTP in 47 cases. The HRTP occurred at 85 +/- 17 Watt (W), which correlated (r = 0.95; P < 0.001) with the LTP2 (84 +/- 17 W) and the LVEFTP (84 +/- 17 W, r = 0.93; P < 0.001). From LTP2 to Pmax a significant decrease in LVEF was found. There was a correlation between the percentage of HRmax at the HRTP and k (r = 0.70), as well as delta LVEF (r = 0.56). CONCLUSIONS: To prevent myocardial overloading, it seems to be useful to determine the HRTP, which indicate the workload where LVEF decreases.     

Quantitation of global and regional left ventricular function by cine magnetic resonance imaging during dobutamine stress in normal human subjects

Magnetic resonance imaging (MRI) provides high-resolution images of the heart. However, physical exercise during MRI is difficult due to space restriction and motion artefacts. To evaluate the feasibility of MRI during stress conditions, dobutamine was used as an alternative to exercise. Haemodynamics, ventricular volumes and wall thickening were measured at rest and during peak dobutamine infusion (15 micrograms.kg-1 x min-1) in 23 normal human subjects. To calculate left ventricular volumes, eight short-axis views were obtained encompassing the left ventricle from base to apex. At six levels, percent systolic wall thickening (%WTh) was measured in 18 segments (20 degrees intervals). Heart rate, systolic and diastolic blood pressures, stroke index, cardiac output and left ventricular ejection fraction increased significantly during dobutamine infusion (all P values < 0.001). In addition, %WTh increased significantly (P < 0.001) during dobutamine compared to the control state at all levels except in the apical and low-left ventricular levels. Both in control conditions and during dobutamine, segmental wall motion analysis showed the highest %WTh at the posterolateral area and the lowest %WTh at the septal region (P < 0.05). MRI clearly identifies wall motion dynamics and provides calculations of segmental wall thickening and haemodynamic parameters. Dobutamine is a useful stress agent by virtue of its safety, operator control and its effects which resemble physical exercise.     

Relation between left ventricular function and oxidative stress in patients undergoing bypass surgery

OBJECTIVE: To determine whether preoperative left ventricular ejection fraction (LVEF) is related to the degree of myocardial oxidative stress during bypass surgery in man. DESIGN: Observational study. SETTING: Tertiary care centre. PATIENTS AND INTERVENTIONS: 31 patients (LVEF range was 20% to 68%) undergoing elective coronary bypass surgery with blood cardioplegic reperfusion were studied. Arterial and coronary sinus blood was collected before aortic cross clamping (T0) and at 0 (T1), 15 (T2), and 30 (T3) minutes after unclamping. Transmural left ventricular biopsies were also obtained from 15 patients at T0 and at T1. MAIN OUTCOME MEASURES: Glutathione and adenine nucleotides were measured in myocardial biopsies, while coronary sinus-artery differences for glutathione, nucleotides, and products of lipid peroxidation were calculated from blood specimens. Creatine kinase (myocardial band; CK-MB) was measured in plasma at four and 12 hours after operation. RESULTS: Myocardial glutathione and adenine nucleotides were correlated (p < 0.02) with preoperative LVEF both at T0 (r = 0.909 and 0.672) and T1 (r = 0.603 and 0.605). Oxidised glutathione released from the heart during reperfusion was inversely correlated with LVEF (r = -0.448, -0.466, and -0461 at T1, T2, and T3, p < 0.01), while reduced glutathione (r = 0.519 and 0.640 at T1 and T2) and glutathione redox ratio (r = 0.647, 0.714, 0.645, and 0.702 at T0, T1, T2, and T3) showed a direct correlation (p < 0.01). Lipid peroxidation at T1 was negatively related to LVEF (r = -0.492). CK-MB was also negatively related to LVEF (r = -0.440 at 4 h and -0.462 at 12 h). CONCLUSIONS: The capacity to counterbalance oxidative burst following ischaemia and reperfusion appears to be related to the functional ability of the heart.     

Reproducibility of right and left ventricular volume measurements by electron-beam CT in patients with congestive heart failure

OBJECTIVE: To assess the efficacy of ultrasound (US) as part of an algorithm to establish the indication for laparotomy in patients with suspected acute appendicitis. DESIGN: Prospective investigation. SETTING: University department of surgery, Germany. SUBJECTS: 669 unselected patients admitted with suspected acute appendicitis. INTERVENTIONS: Clinicopathological and procedural diagnoses of the algorithm were evaluated by correlating clinical and US findings with the results of laparotomy in 171 patients of whom 143 had acute appendicitis (prevalence 21%), and clinical as well as follow up data in the remainder. MAIN OUTCOME MEASURES: The major clinicopathological variables were accuracy and positive predictive value; the rate of negative laparotomies and that of bad diagnostic errors served as the main procedural variables. RESULTS: The overall sensitivity, specificity, and accuracy of the clinical diagnosis were 0.503, 0.950, and 0.855, respectively (positive predictive value: PPV 0.734, negative predictive value: NPV 0.875), those of ultrasound: 0.797, 0.967, and 0.931 (PPV 0.870, NPV 0.946); and 0.853, 0.927, and 0.940 at the end of the algorithm (PPV 0.762, NPV 0.958). However, the algorithm would have resulted in a significant increase in the rate of unnecessary laparotomies (from 13% to 16%). A revised clinical algorithm gave an overall diagnostic accuracy of 0.940 (p < 0.001) together with a low rate of negative laparotomies (11%, p < 0.01) and a significantly reduced number of diagnostic errors (from 71 to 21, p < 0.001). CONCLUSION: Ultrasonography enabled us to diagnose acute appendicitis in more patients more often and more quickly than clinical evaluation alone, suggesting that US may produce a better outcome. The revised clinical algorithm may be helpful in the study of US in patients with suspected acute appendicitis in prospective randomised controlled clinical trials.     

Can indices of left ventricular function be applied to the right ventricle?

This article compares conventional indices of contractile function in the right and left ventricles. The low operating pressures and left ventricles. The low operating pressures and complex geometry complicate evaluation of right ventricular function. However, when the characteristics of its vascular load are taken into account, the complex right ventricular chamber has pump properties that are similar to the high pressure left ventricular chamber.