Colloid osmotic pressure in pulmonary edema clearance with furosemide

After tripling of baseline lung water (EVLW), decreasing wedge pressure (PWP) alone for two hours did not decrease EVLW. In 11 of 16 dogs, triple baseline EVLW and a decrease in plasma colloid osmotic pressure (COP) from 21.1 +/- 0.8 to 17.8 +/- 0.8 mm Hg resulted from left atrial balloon inflation at PWP of 28 to 30 mm Hg. With subsequent lowering of PWP to 10 mm Hg, intravenously administered furosemide (1 mg/kg) was given to these 11 dogs. One half hour after furosemide, shunt decreased slightly without decreasing EVLW in all 11 dogs, but by two hours, seven dogs (group 1) decreased EVLW (from 23.2 +/- 1.8 to 11.1 +/- 1.4 ml/kg) and shunt (37.4 +/- 2.0 to 12.9 +/- 2.9 percent), while four dogs (group 2) did not (EVLW: 22.3 +/- 1.4 to 22.5 +/- 0.6 ml/kg: shunt, 36.8 +/- 1.7 to 36.5 +/- 1.9 percent). Group 1 had diuresis, maintained normal blood urea nitrogen and creatinine levels, and increased COP from 17.7 +/- 0.7 to 23.6 +/- 0.5 mm Hg while group 2 was oliguric with elevated BUN and creatinine values and showed no change in COP (17.9 +/- 0.9 to 18.3 +/- 0.6 mm Hg) after furosemide. After decreasing PWP in massive pulmonary edema (triple baseline EVLW), furosemide appeared to enhance edema clearance by changes in COP with diuresis.     

Pericardial effusion causes interstitial pulmonary edema in dogs

The pulmonary effects of pericardial effusion were studied in eight anesthetized dogs, with emphasis on lung mechanics, O2 exchange, and extravascular thermal lung volume (ETV) accumulation, while warm saline was instilled into the pericardium to elevate pericardial pressure. The results were compared with those from four time-controlled and sham-operated dogs. ETV, as measured by a double-indicator technique, increased from 8.1 +/- 0.8 ml/kg at a pericardial pressure of 0 mm Hg to 12.9 +/- 2.1 ml/kg at 11.0 mm Hg (p less than .01). In the control group, ETV increased from 6.5 +/- 0.7 to 8.2 +/- 0.5 ml/kg over an equal time span. This increase in ETV in the experimental dogs was inversely related to pulmonary compliance, which decreased by 29% as ETV increased (p less than .05), whereas in the time-controlled group of animals it decreased by 8.8%. Arterial PO2 did not deteriorate during the protocol in either group. Histologic examination showed increased interstitial fluid, but neither alveolar fluid nor septal edema, and gravimetric measurements of lung liquid were also consistent with interstitial fluid accumulation in experimental but not control animals. These findings are concordant with the clinical observation that alveolar edema is rarely seen in the presence of pericardial tamponade. Conceivably, progression from interstitial to alveolar edema did not occur both because of the low pulmonary blood flow that occurs as part of pericardial tamponade physiology and/or because the hydrostatic pressures were not elevated enough to produce higher rates of fluid transudation.     

持续气道正压通气对急性心源性肺水肿犬呼吸及循环功能的影响

目的研究持续气道正压(CPAP)通气对急性心源性肺水肿(ACPE)犬呼吸及循环功能的影响。方法分别监测10条犬健康状态及ACPE发生后自主呼吸、5cmH2O(1cmH2O=0.098kPa)、10cmH2O、15cmH2OCPAP时的胸腔负压(Pt)、中心静脉压(CVP)、心输出量(CO)、平均动脉压(BPm)、肺动脉楔压(PAWP)。结果与健康状态相比,ACPE犬呼吸增强、增快,Pt由-(4.90±0.09)cmH2O上升至-(10.90±0.75)cmH2O,CVP由(10.1±0.4)mmHg下降至(8.0±0.7)mmHg,CO由(1.52±0.13)L/min下降至(0.85±0.09)L/min,PAWP升高(P均<0.05)。CVP与Pt变化呈正相关(r=0.78,P<0.01)。5及10cmH2OCPAP时Pt值恢复至-(6.53±0.11)cmH2O和-(5.14±0.25)cmH2O,呼吸形式基本恢复正常,CVP升至(11.6±0.7)mmHg和(14.2±0.2)mmHg,CO增加至(1.45±0.11)L/min和(1.24±0.11)L/min,其中5cmH2OCPAP组PAWP下降(P均<0.05)。15cmH2OCPAP时,呼吸浅快,Pt为-(0.82±0.37)cmH2O,CO为(0.82±0.07)L/min,其他血流动力学指标皆恶化(P均<0.05)。结论犬ACPE发生时,呼吸运动显著增强,Pt升高,并导致CVP和CO的下降;适当CPAP通过改善呼吸功能,调节Pt改善ACPE犬的心功能。     

Pulmonary artery wedge pressure and extravascular lung water in patients with acute cardiogenic pulmonary edema requiring mechanical ventilation

This study describe the values of pulmonary artery wedge pressure (PAWP) and the extravascular lung water (EVLW) index in patients with acute cardiogenic pulmonary edema who require mechanical ventilation. Ten consecutive patients with acute cardiogenic pulmonary edema who required mechanical ventilation were studied. Cardiac index was determined with thermodilution. Central venous pressure and PAWP were measured with a pulmonary artery catheter. EVLW index was determined with the thermal dye dilution technique, using a commercially available computer system. Measurements were made at regular preset intervals after the initiation of mechanical ventilation. PAWP was normal at baseline (11.6+/-0.9 mm Hg, range 8 to 17) and did not change. EVLW index was elevated at baseline (13.7+/-1.5 ml/ kg) and decreased to a normal value after 24 hours (8.6+/-1.2 ml/kg, p = 0.02). Concomitantly cardiac index increased from 2.61+/-0.24 to 3.61+/-0.14 L/min/m2 (p = 0.05). There was no correlation between PAWP and EVLW index. Fluid balance was +1,221+/-908 ml after 24 hours and there was a weight gain of 0.88+/-1.06 kg after 24 hours. Thus, patients with acute cardiogenic pulmonary edema requiring mechanical ventilation may have a normal PAWP after mechanical ventilation has been initiated. In a hemodynamic unstable situation, these patients may require fluid challenges to improve cardiac output, despite the presence of pulmonary edema. The pulmonary edema, measured as EVLW index, resolves rapidly when cardiac performance improves, despite positive fluid balances and weight gain in the first 24 hours.     

Hypoalbuminemia in elderly patients with acute diastolic heart failure

OBJECTIVES: This study evaluated the relative contribution of serum colloid osmotic pressure (COP) lowering and pulmonary artery wedge pressure (PAWP) elevation in the pathogenesis of pulmonary edema in patients with systolic or isolated diastolic heart failure (DHF). BACKGROUND: The role of hypoalbuminemia and the resulting low COP have been shown in some patients with acute systolic heart failure (SHF).Colloid osmotic pressure and PAWP were determined in 100 patients with acute heart failure (HF) (56 with DHF and 44 with SHF; mean age, 78 +/- 12 years), in 35 patients with acute dyspnea from pulmonary origin, and in 15 normal controls. Pulmonary artery wedge pressure was estimated using transthoracic Doppler echocardiography. RESULTS: Colloid osmotic pressure was significantly lower in the DHF group (20.5 +/- 5 mm Hg) than in the SHF group (24.2 +/- 3.7 mm Hg, p < 0.001), pulmonary disease group (25.1 +/- 4.2 mm Hg, p < 0.001), or normal control group (24.7 +/- 3 mm Hg). Low COP resulted from hypoalbuminemia due to age, malnutrition, and sepsis. Pulmonary artery wedge pressure was significantly higher in patients with SHF (26 +/- 6.3 mm Hg) than in the patients with DHF (20.3 +/- 7 mm Hg, p < 0.001) and was significantly higher in the patients with DHF than in the patients with pulmonary disease (13 +/- 4.2 mm Hg, p < 0.001). The COP-PAWP gradient was similar in patients with SHF (-1.6 +/- 7.1 mm Hg) and patients with DHF (0.7 +/- 6 mm Hg). CONCLUSIONS: Frequent hypoalbuminemia resulting in low COP facilitates the onset of pulmonary edema in patients with DHF who usually have lower PAWP than patients with SHF.     

Rapid flow rates for the resuscitation of hypovolemic shock

Nine dogs were hemorrhaged to approximately 40% of their blood volume and then were resuscitated with a crystalloid solution (Normosol) at various flow rates. Three study groups with three dogs in each group were resuscitated at 15 mL/min/kg (Group 1), 6 mL/min/kg (Group 2), and 4 mL/min/kg (Group 3). Central venous pressure (CVP), pulmonary artery wedge pressure (PAWP), mean arterial pressure, and cardiac output (CO) were monitored during the hemorrhage and the resuscitation from shock. During the infusion of fluids, Group 1 animals demonstrated an elevation of the PAWP of 31 mm Hg and elevation of CVP to 23.2 mm Hg; CO rose to 8.4 L/min. In Group 2 animals CO rose to 6.1 L/min; CVP was 10.5 mm Hg; and PAWP was 25 mm Hg. Group 3 animals had a rise in CO to 5 L/min; CVP and PAWP rose to 4.5 mm Hg and 6.8 mm Hg, respectively. In this experimental shock study, infusion of crystalloids at 6 mL/min/kg appeared to result in an improved physiologic response, although no statistical difference was demonstrated. Further studies are necessary to demonstrate the optimum flow rate for resuscitation of hypovolemic shock using crystalloids.     

Extravascular lung water in patients with septic shock during a fluid regimen guided by cardiac index

BACKGROUND: To elucidate whether patients with a septic shock develop pulmonary edema in a treatment protocol in which volume loading is guided by its effect on the cardiac output, rather than by preset values of pulmonary artery wedge pressure (PAWP). METHODS: 15 consecutive patients with the diagnosis of septic shock were studied in a prospective observational study. Cardiac output, PAWP and extravascular lung water index (EVLWI) were determined at regular intervals during the first 24 h of treatment. Fluid challenges were given if MAP was <80 mm Hg and/or CI was <4.5 l/min/m(2), and PAWP was <16 mm Hg. Further fluid challenges were only given if the preceding fluid challenge resulted in an increase in CI of more than 10% and PAWP was still <16 mm Hg. RESULTS: EVLWI was slightly above normal (10.4+/-1.2 ml/kg) and did not change during the treatment protocol. One third of the patients had an initial PAWP>16 mmHg. In these patients, EVLWI was significantly higher than in patients with an initial PAWP <16 mm Hg (14.1+/-1.1 ml/kg versus 10.0+/-0.9 ml/kg, P=0.026). No significant correlation was found between PAWP and EVLWI. CONCLUSION: In this study, patients with septic shock did not develop pulmonary edema during the first 24 h of treatment, when their fluid regimen was guided by the effects on cardiac output.     

Role of platelet-activating factor in pulmonary edema after coronary ligation in dogs.

To evaluate whether PAF is related to the precipitation of pulmonary edema after myocardial ischemia, we studied the effect of a specific PAF antagonist, CV-6209, on the extravascular lung water level measured by the thermal-dye double indicator dilution method, ETV, after coronary ligation in dogs. Eight dogs served as sham control animals (group 1). The proximal left anterior descending coronary artery was ligated for 45 min in eight dogs (group 2), and the coronary artery was ligated after pretreatment with CV-6209 (1 mg/kg) in eight dogs (group 3). The ETV increased significantly after coronary ligation in groups 2 and 3. The amount of increase in ETV in group 2 was significantly larger than in group 3. Thus, CV-6209 can prevent the accumulation of extravascular lung water after coronary ligation without producing changes in pulmonary vascular dynamics, indicating that PAF may play an important role in pulmonary edema after myocardial ischemia.     

Hemodynamic abnormalities during coronary angiography: comparison of Hypaque-76, Hexabrix, and Omnipaque-350

The hemodynamic effects induced by coronary angiography in dogs with low osmolar ionic dimer Hexabrix (HB) and nonionic Omnipaque-350 (OM) were compared to the standard ionic contrast medium, Hypaque-76 (H76), both in the normal heart and in one with simulated severe cardiac disease. Left coronary angiography was performed in 12 "normal" closed-chest dogs with 10-cc injections of H76, HB, and OM in a randomized, blinded fashion. The maximal change in the left ventricular (LV) systolic pressure (SP), mean aortic pressure (MAP), left ventricular end diastolic pressure (LVEDP), and LV dp/dt were recorded. The LVSP and MAP fell 30 +/- 3 mm Hg and 26 +/- 4 mm Hg with H76, 22 +/- 2 mm Hg and 19 +/- 2 mm Hg with HB, and 7 +/- 1.5 mm Hg and 5 +/- 1 mm Hg with OM (P less than .001). The LVEDP increased 4.8 +/- 0.5 mm Hg with H76, 3 +/- 0.5 mm Hg with HB, but only 0.2 mm Hg with OM (P less than .001). The LV dp/dt decreased 392 +/- 63 mm Hg/sec with H76 and 235 +/- 21 mm Hg/sec with HB, but increased 411 +/- 50 mm Hg with OM (P less than .001). In eight additional open-chest dogs, left coronary angiography was performed 1 hr after occlusion of the proximal LAD coronary artery and in the presence of a critical circumflex coronary artery (CX) stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bradykinin contribution to renal blood flow effect of angiotensin converting enzyme inhibitor in the conscious sodium-restricted dog

We examined the relative contribution of renin-angiotensin system blockade and bradykinin potentiation to the renal hemodynamic effect of the angiotensin converting enzyme inhibitor enalaprilat in sodium-deprived dogs. Six conscious dogs instrumented for monitoring of blood pressure (BP) and renal blood flow (RBF) were employed in five groups of experiments. In group 1, enalaprilat alone was administered, and it decreased BP by -24 +/- 3 mm Hg and increased RBF by 135 +/- 15 ml/min. During a constant intravenous infusion of saralasin (group 2), enalaprilat decreased BP by -7 +/- 3 mm Hg and increased RBF by 84 +/- 7 ml/min (delta BP and delta RBF, p less than 0.01 vs. group 1 by analysis of variance). During a constant intrarenal arterial infusion of saralasin (group 3), the respective changes in BP and RBF after enalaprilat were -10 +/- 3 mm Hg and 69 +/- 12 ml/min, and these results did not differ from those of group 2. The infusion of saralasin intravenously or intrarenal arterially decreased BP slightly and increased RBF. In the presence of an intravenous infusion of a specific bradykinin antagonist, D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg.TFA (B5630) (group 4), enalaprilat decreased BP by -28 +/- 4 mm Hg and increased RBF by 82 +/- 24 ml/min (delta RBF, p less than 0.01 vs. group 1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary pressure-flow relations in hypertensive left ventricular hypertrophy. Comparison of intact autoregulation with physiological and pharmacological vasodilation in the dog

Coronary pressure-flow relations during autoregulated and vasodilated flow states were compared between eight dogs with renovascular hypertension and left ventricular hypertrophy and 12 normal dogs. Each relation was constructed from serial steady-state measurements of end-diastolic coronary pressure and flow during perfusion of the circumflex artery by an extracorporeal circuit at controlled diastolic pressures of 20-200 mm Hg. Autoregulated pressure-flow relations were compared at three levels of myocardial oxygen demand: resting, high (dobutamine 10 micrograms/kg/min), and low (propranolol 2.5 micrograms/kg/min). Autoregulatory capacity was assessed by calculation of closed-loop flow gain. At each level of myocardial oxygen demand, the lower limit of autoregulation occurred at higher perfusion pressures in the hypertrophy group (rest 65 +/- 3, high 92 +/- 4, low 66 +/- 4 mm Hg) than in the normal group (rest 53 +/- 2, p less than 0.05; high 75 +/- 5, p less than 0.05; low 51 +/- 3 mm Hg) (p less than 0.05). Maximum autoregulatory gain was similar in the normal and hypertrophy groups during resting and low myocardial oxygen demand but was reduced in the hypertrophy group during dobutamine studies. When coronary flow decreased below the lower limit of autoregulation, systolic shortening was reduced in both normal and hypertrophy groups. However, as the autoregulatory limits were at higher pressures in the hypertrophy group, shortening in this group deteriorated at perfusion pressures that did not affect the normal heart. Coronary pressure-flow relations during physiological (peak hyperemia after 15-second flow occlusion) and pharmacologica (intracoronary adenosine 400 micrograms/min) vasodilation was curvilinear and fitted by quadratic regression. During hyperemic vasodilation, maximal conductance per unit mass of myocardium was less in the hypertrophy group over a wide range of perfusion pressures. At a diastolic perfusion pressure of 80 mm Hg, maximum conductance was 4.6 +/- 0.5 ml/min/100 g/mm Hg in the normal group and 3.4 +/- 0.4 ml/min/100 g/mm Hg (p less than 0.05) in the hypertrophy group. Intracoronary adenosine elicited further vasodilation in both groups, but maximum conductance remained less in the hypertrophy group (8.5 +/- 1.7 ml/min/100 g/mm Hg at a perfusion pressure of 80 mm Hg) than in the normal group (13.5 +/- 2.0 ml/min/100 g/mm Hg) (p less than 0.05). Maximal coronary flow reserve is reduced in left ventricular hypertrophy, with a consequent shift of the lower limit of autoregulation to higher perfusion pressures. Thus, as coronary perfusion pressure is decreased, coronary flow and myocardial shortening become impaired at higher     

Incidence of early tolerance to hemodynamic effects of continuous infusion of nitroglycerin in patients with coronary artery disease and heart failure

Sustained therapy with nitroglycerin (NTG) has been reported to provoke the development of early tolerance. Because continuous intravenous NTG infusion is commonly used in patients with coronary artery disease and heart failure, we evaluated the incidence of early tolerance developed within the first 24 hr of therapy in 31 responders to NTG. After documentation of response to NTG, defined as a 10 mm Hg or greater or a 30% or greater reduction in mean pulmonary arterial wedge pressure (PAWP), 16 patients were blindly, randomly assigned to receive placebo and 15 patients were continued on same-dose NTG. Both groups showed an identical fall in PAWP at peak NTG titration (11 +/- 4 mm Hg). Discontinuation of NTG in the placebo group resulted in a rapid increase in PAWP to levels not significantly different from baseline (19 +/- 5 mm Hg at 2 hr vs 23 +/- 6 mm Hg at baseline; p = NS). In the NTG group, PAWP fell from 27 +/- 9 to 14 +/- 7 mm Hg, was 16 +/- 9 mm Hg at 2 hr (p less than .05 vs baseline), and continued to be significantly lower than baseline for 8 hr; however, due to attenuation of effect, PAWP values at 12, 20, and 24 hr were not significantly different from placebo or baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of 5-HT2 receptor inhibition in pulmonary embolization

We examined the role of serotonin at the 5-HT2 receptor site after pulmonary embolization for changes in hemodynamics, gas exchange, and lung water. Pulmonary embolization was induced using 0.75 gm/kg autologous clot in anesthetized artificially ventilated dogs. Pulmonary vascular resistance rose by 5 min from 3.4 +/- 1.5 to 14.2 +/- 2.1 mm Hg/liter/min (p less than 0.001), arterial oxygenation decreased from 91 +/- 5 to 68 +/- 5 mm Hg (p less than 0.01), platelet count decreased from 201 +/- 64 to 141 +/- 32 ml X 10(3), and the wet to dry weight lung ratio increased from 2.59 +/- 0.34 to 4.21 +/- 0.21 (p less than 0.001). Inhibition by ketanserin, a selective serotonergic inhibitor at the 5-HT2 receptor site substantially attenuated the increase in pulmonary vascular resistance from 3.6 +/- 1.4 to 8.0 +/- 2.5 mm Hg/liter/min, ablated the hypoxemia and platelet reduction and inhibited the formation of pulmonary edema. Infusion of serotonin simulated only some of the above changes as the pulmonary vascular resistance increased from 3.16 +/- 1.6 to 13.5 +/- 4.1 mm Hg/liter/min (P less than 0.01) and the oxygenation decreased from 96 +/- 5 to 57 +/- 4 mm Hg (P less than 0.01). Serotonin infusion, however, did not cause pulmonary edema. The administration of ketanserin ablated the increase in pulmonary vascular resistance and the hypoxemia following serotonin infusion. We conclude that following pulmonary embolization, serotonin at the 5-HT2 receptor is responsible for the fall in PaO2 and partially responsible for the increased pulmonary vascular resistance. Although ketanserin inhibits the formation of pulmonary edema following pulmonary embolization, serotonin does not seem to be directly responsible.     

Sodium and volume depletion activates neurogenic mechanisms in renal hypertensive dogs

The acute response to ganglionic blockade (hexamethonium bromide, 30 mg/kg, i.v.) was used to evaluate the neurogenic contributions to mean arterial pressure maintenance in the conscious one-kidney, one clip hypertensive dog. Approximately 2 hours (112 minutes) after ganglionic blockade, captopril (10 mg/kg, i.v.) was given to block the renin-angiotensin system. Hypertensive animals were studied 3 days after clipping (group 2) or 2 to 4 weeks after clipping (groups 3 and 4). Groups 2 and 3 were fed a regular sodium diet, but group 4 animals were sodium and volume depleted. Normotensive control animals (group 1) were fed a regular sodium diet. On the day of the acute experiment the baseline blood pressures measured in group 2 (151 +/- 10 mm Hg, n = 5), group 3 (154 +/- 5 mm Hg, n = 7), and group 4 (160 +/- 8 mm Hg, n = 7) were not different (p greater than 0.05) from each other, but all were elevated (p less than 0.05) compared with the group 1 animals (106 +/- 3 mm Hg, n = 8). Also, there were no significant differences (p greater than 0.05) in the baseline plasma catecholamine levels among the three hypertensive groups. Ganglionic blockade produced a greater fall in blood pressure (p less than 0.05) in the sodium/volume-depleted dogs of group 4 (-35 mm Hg) than in group 1 (-10 mm Hg), group 2 (-3 mm Hg), or group 3 (-12 mm Hg) animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Systolic and diastolic dysfunction during atrial pacing in conscious dogs with left ventricular hypertrophy

To determine the extent to which the hypertrophied left ventricle responds to the chronotropic stress induced by graded atrial pacing rates, we studied conscious, chronically instrumented dogs with severe compensated pressure overload left ventricular (LV) hypertrophy induced by aortic banding in puppies 8-10 weeks of age. At 1-2 years, dogs with severe LV hypertrophy (LV free wall/body wt ratio 6.8 +/- 0.6 g/kg) and sham-operated littermates (LV free wall/body wt ratio 4.0 +/- 0.3 g/kg) were instrumented with ultrasonic dimension crystals to measure LV short axis internal diameter and wall thickness, miniature LV pressure transducers, and aortic and LV catheters. During atrial pacing (240 beats/min) in eight control dogs, LV pressure did not change from 119 +/- 2 mm Hg, and mean velocity of circumferential fiber shortening (VCF) did not change from 1.25 +/- 0.09/sec. In seven dogs with LV hypertrophy, atrial pacing (240 beats/min) decreased systolic LV function; that is, LV systolic pressure decreased (p less than 0.01) by 65 +/- 12 from 254 +/- 14 mm Hg, and VCF decreased (p less than 0.01) by 0.19 +/- 0.03 from 0.97 +/- 0.15/sec. Diastolic dysfunction was also observed in the dogs with LV hypertrophy. In the control dogs during atrial pacing (240 beats/min), LV end-diastolic pressure decreased (p less than 0.01) by 8 +/- 1 from 9 +/- 1 mm Hg, end-diastolic stress decreased (p less than 0.01) by 18 +/- 2 from 22 +/- 2 g/cm2, and the radial myocardial stiffness constant did not change from 5.6 +/- 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiopulmonary bypass in a model of acute myocardial infarction and cardiac arrest

Cardiopulmonary bypass (CPB) reperfusion has demonstrated improved resuscitation rates in ventricular fibrillation cardiac arrest models. To investigate the effectiveness of CPB reperfusion in an ischemic cardiac arrest setting, simulating the clinical scenario of myocardial ischemia preceding sudden cardiac death, we developed a canine model of acute myocardial infarction followed by ventricular fibrillation. Sixteen dogs were randomly assigned to two groups. Group 1 (eight) had ventricular fibrillation induced without left anterior descending coronary artery occlusion. Group 2 (eight) had a thrombogenic copper coil placed in the left anterior descending artery and showed ECG evidence of acute myocardial infarction before induction of ventricular fibrillation. CPR commenced after eight minutes of ventricular fibrillation. Epinephrine 0.05 mg/kg and NaHCO3 1.0 mEq/kg were administered at ten minutes. CPB was begun at 12 minutes and continued for one hour. Myocardial ischemic and necrotic areas were determined in four-hour survivors by dual histochemical staining. All animals were resuscitated; all eight group 1 and six of eight group 2 animals survived to four hours. With the onset of CPB, coronary perfusion pressures increased significantly by 68.6 +/- 31.8 (SD) mm Hg in group 1 and 56.2 +/- 34.6 mm Hg in group 2 over those obtained with CPR (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of baroreceptor denervation on the inhibition of renin release by vasopressin

Previous studies have suggested that the inhibition of renin secretion by acute administration of vasopressin in conscious dogs results from a reflex reduction in renal nerve activity. In the present investigation, this hypothesis was tested by studying the effect of total baroreceptor denervation or selective low pressure baroreceptor denervation on the suppression of PRA by vasopressin in conscious, chronically prepared dogs. In eight sham-operated dogs, a 45-min infusion of vasopressin (2.0 ng/kg.min, iv) decreased PRA from 10.5 +/- 1.9 to 5.9 +/- 1.0 ng/ml.3 h (P less than 0.01). Mean arterial pressure did not change (110 +/- 10 to 107 +/- 7 mm Hg), but heart rate decreased from 84 +/- 9 to 69 +/- 8 beats/min (P less than 0.05). In contrast, vasopressin infusion failed to significantly decrease PRA in seven sinoaortic/cardiac denervated dogs (9.5 +/- 1.7 to 7.4 +/- 2.0 ng/ml.3 h), although decreases did occur in three of the dogs. Mean arterial pressure increased from 104 +/- 5 to 125 +/- 6 mm Hg (P less than 0.01), but heart rate did not change (112 +/- 4 to 107 +/- 5 beats/min). When renal perfusion pressure was maintained at the preinfusion level in three sinoaortic/cardiac denervated dogs, vasopressin infusion failed to decrease PRA (2.3 +/- 0.6 to 2.4 +/- 0.6 ng/ml.3 h). In six cardiac denervated dogs, vasopressin infusion decreased PRA from 5.3 to 0.9 to 3.1 +/- 0.7 ng/ml.3 h (P less than 0.01). Results obtained with two lower doses of vasopressin (0.5 and 1.0 ng/kg.min) were generally similar to the responses observed during infusion at 2.0 ng/kg.min. Angiotensin II (5.0 ng/kg.min) suppressed PRA in all groups of dogs. These experiments demonstrate that the inhibition of renin secretion by acute administration of vasopressin in conscious dogs is prevented by total baroreceptor denervation, but not by denervation of the low pressure baroreceptors alone. These results suggest that the suppression of renin release by vasopressin is a reflex response resulting from activation of the high pressure baroreceptors.     

Cisapride effects on canine lower esophageal sphincter under various pharmacological pretreatments.

Cisapride (Ci) stimulates lower esophageal sphincter pressure (LESP). This study aims to test whether the effect of Ci on LES in vivo is still present if LES is relaxed by atropine (Atr) and nifedipine (Nife) prior to the administration of Ci. LESP was continuously recorded by manometry in 6 mongrel dogs with esophageal fistulae. Ci was given as an intravenous bolus following either Atr (40 micrograms/kg i.v.) or Nife (20 mg subl.) at the time of maximal LESP decrease (5/15 min later). Basal LES values ranged between 24.5 +/- 2.5 mm Hg (Atr group) and 23.8 +/- 3.9 mm Hg (Nife group). Following Atr, LESP decreased to a minimal value of 7.0 +/- 0.5 mm Hg; after Nife LESP decreased to a minimal value of 12.3 +/- 2.0 mm Hg. Additional administration of Ci was not able to reincrease LESP. We conclude that the action of Ci on LES cannot take place if (1) muscarinergic receptors are blocked by Atr and (2) the Ca2+ activation system is blocked by Nife. Our results suggest that the action of cisapride on LES, as its action on gastrointestinal smooth muscle cells, is mediated by postsynaptic enhancement of acetylcholine release.     

Acute hemodynamic effect of oral nifedipine in severe chronic congestive heart failure

The temporal hemodynamic effects of oral nifedipine after a single dose of 20 to 40 mg were evaluated in 11 patients with severe chronic congestive heart failure (left ventricular ejection fraction 0.22 +/- 0.7 [mean +/- standard deviation]). Nifedipine significantly reduced systemic vascular resistance, from 1,850 +/- 493 to 1,315 +/- 398 dynes s cm-5 at 1 hour (29%), to 1,410 +/- 246 at 3 hours and to 1,523 +/- 286 at 6 hours (p less than 0.05). Cardiac index increased 21%, from 2.07 +/- 0.46 to 2.51 +/- 0.83 liters/min/m2 at 1 hour, to 2.38 +/- 0.53 liters/min/m2 at 3 hours (p less than 0.05) and to 2.24 +/- 0.41 liters/min/m2 at 6 hours. The group response of stroke volume to nifedipine was smaller. A peak increase of 17% was seen 3 hours after initiation of therapy (22.6 +/- 7.2 versus 25.5 +/- 6.1 ml/m2). This difference did not reach statistical significance. Mean blood pressure declined significantly, from 94 +/- 20 to 80 +/- 13 mm Hg at 1 hour, to 83 +/- 15 mm Hg at 3 hours and to 86 +/- 17 mm Hg at 6 hours (p less than 0.05) and was associated with no significant change in heart rate. The marked decrease in blood pressure resulted in a decrease in rate-pressure product from 12,272 +/- 4,230 to 10,500 +/- 2,074 mm Hg/min at 1 hour, to 10,374 +/- 2,735 mm Hg/min at 3 hours and to 11,047 +/- 3,813 mm Hg/min at 6 hours (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute hemodynamic and hormonal effects of ramipril in chronic congestive heart failure and comparison with captopril

Acute hemodynamic and hormonal responses to ramipril in comparison with captopril were studied in 10 patients with moderate to severe congestive heart failure in an open, randomized study. Both drugs were given to 5 patients each in 2 increasing doses on 2 successive days. After 5 mg of ramipril angiotensin converting enzyme (ACE) activity was significantly decreased during 24 hours with a maximum decrease 4 hours after administration. Mean arterial blood pressure decreased from 84 +/- 5 to 62 +/- 5 mm Hg at 4 hours and 71 +/- 4 mm Hg at 12 hours, respectively, after this dose. Capillary wedge pressure decreased from 19 +/- 1 mm Hg to 13 +/- 1 mm Hg at 4 hours with a maximum increase in cardiac output from 3.8 +/- 0.3 liters/min to 4.4 +/- 0.3 liters/min at 2 hours. No significant cardiac effects were present 8 hours after administration. After 10 mg of ramipril, cardiac and hormonal effects showed a quicker onset of action and longer duration compared with the 5 mg dose. Mean arterial pressure decreased to 61 +/- 6 mm Hg. Similar effects were seen after captopril, but with a significantly shorter duration. Mean arterial pressure decreased from 82 +/- 4 mm Hg to 64 +/- 5 mm Hg after 12.5 mg and to 58 +/- 6 mm Hg after 25 mg of captopril. In patients with congestive heart failure ramipril has the hemodynamic profile of a long-acting and potent ACE inhibitor. Significant cardiac effects are present during 4 to 8 hours and ACE activity is still significantly inhibited 24 hours after a single dose of ramipril.(ABSTRACT TRUNCATED AT 250 WORDS)