Thomas R. Vrobel

Role of the renin-angiotensin system in the systemic vasoconstriction of chronic congestive heart failure.

SUMMARY In 15 patients with severe chronic left ventricular failure, plasma renin activity (PRA) ranged widely, from 0.2-39 ng/ml/hr. The level of PRA was unrelated to cardiac output (CO) or pulmonary artery wedge pressure (PWP), but was slightly negatively correlated with mean arterial pressure (MAP) (r = -0.45) and systemic vascular resistance (SVR) (r = -0.40). After infusion of the angiotensin converting enzyme inhibitor teprotide (SQ 20,881) PWP fell from 26.3 ± 1.3 (SEM) to 20.3 ± 1.4 mm Hg (P < 0.001), CO rose from 3.94 ± 0.23 to 4.75 ± 0.31 1/min (P < 0.001), MAP fell from 87.5 ± 3.8 to 77.9 ± 4.1 mm Hg (P < 0.001) and SVR from 1619 ± 148 to 1252 ± 137 dyne-sec-cm-5 (P < 0.001). The fall in MAP and in SVR was significantly correlated with control PRA (r = 0.68 and r = 0.58, respectively). When subjects were divided on the basis of control PRA the hemodynamic response to teprotide was greatest in the high renin group. PRA rose after teprotide (8.7 ± 3.4 to 37.9 + 7.7 ng/ml/hr, P < 0.05) but plasma norepinephrine fell (619.1 ± 103.6 to 449.7 ± 75.7, P < 0.05). The renin-angiotensin system thus appears to have an important role in the elevated SVR in some patients with heart failure. Chronic inhibition of converting enzyme should be explored as a possible therapeutic approach.

Abnormalities in myocardial perfusion during tachycardia in dogs with left ventricular hypertrophy: metabolic evidence for myocardial ischemia.

This study tested the hypothesis that in the chronically hypertrophied left ventricle pacing stress may cause abnormalities of perfusion that result in myocardial ischemia. Left ventricular hypertrophy (LVH) was produced by banding the ascending aorta of 10 dogs at 6 weeks of age, and studies were carried out after the animals had reached adulthood and when mean left ventricular/body weight ratio was 74% greater than in eight control dogs. Myocardial blood flow was measured with microspheres during pacing at 100, 200, and 250 beats/min, while aortic and coronary sinus blood samples were obtained for determination of concentrations of lactate and the adenosine metabolites inosine and hypoxanthine. In the control dogs, increasing heart rates were associated with an increase in mean myocardial blood flow while subendocardial flow was maintained at a level equal to or greater than subepicardial flow. Myocardial lactate uptake ranged from +60% to -5%, and adenosine metabolites were not detected in coronary sinus blood (less than 0.5 microM/l). In four dogs that underwent aortic banding no production of lactate or adenosine metabolites was observed at any heart rate; in these animals subendocardial flow was maintained at a level equal to or greater than subepicardial flow at all pacing rates. The remaining six dogs with LVH demonstrated net lactate production significantly greater than control during pacing at 250 beats/min; five of these six animals also produced adenosine metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyponatraemia as a marker for high renin heart failure.

The factors that might activate the renin-angiotensin system in treated heart failure were explored. Serum Na+ correlated inversely with plasma renin activity. The degree of congestive heart failure measured by right atrial pressure, pulmonary capillary wedge pressure, cardiac index, and systemic vascular resistance did not correlate with plasma renin activity. Similarly, renal function as measured by blood urea nitrogen, creatinine, and urinary Na+ excretion did not correlate with plasma renin activity. In a prospectively screened group, seven patients with congestive heart failure who were found to be hyponatraemic had plasma renin activities greater than 15 ng/ml per h. Serial determinations in one patient showed plasma renin activity to vary inversely with the serum Na+. It is concluded that serum sodium can be used to identify those patients with congestive heart failure who have a high plasma renin activity. The value of identifying these high renin heart failure patients was seen in their response in four cases to specific therapy with a converting enzyme inhibitor.

Rapid suppression of complex ventricular arrhythmias with high-dose oral amiodarone

Although amiodarone is effective for the suppression of complex ventricular arrhythmias, a major problem with its use is the long delay between the initiation of therapy and the onset of effective suppression of arrhythmia. To test the hypothesis that rapid loading with oral amiodarone to a target serum concentration can overcome much of this delay, eight patients with refractory, sustained, hemodynamically compromising ventricular arrhythmias and 10 patients with potentially life-threatening ventricular arrhythmias were treated with a flexible, very high dose, oral loading protocol (800 to 2000 mg two to three times a day). Dosage was adjusted on the basis of amiodarone serum concentrations to maintain the trough serum concentrations between 2.0 and 3.0 micrograms/ml. Comparison of 24 hr Holter electrocardiograms obtained before and during therapy revealed statistically significant reductions in premature ventricular complexes (PVCs) and paired PVCs beginning the first day of therapy and a reduction in ventricular tachycardia (VT) beginning the second day. By day 2, four of eight patients with sustained VT and six of 10 patients with nonsustained VT showed no VT. Pulmonary arterial catheterization during the first 24 hr (mean amiodarone dose 3933 mg) revealed no significant hemodynamic alterations. Minor side effects were common (10 patients) but major side effects were rare (one patient). High-dose oral loading with amiodarone utilizing serum concentration guidelines is a safe and effective method of rapidly controlling life-threatening arrhythmias in selected patients.

Effects of exercise on blood flow in the hypertrophied heart.

Abstract This study was carried out to examine the response of regional myocardial blood flow to exercise in normal dogs and in dogs with left ventricular hypertrophy. Left ventricular hypertrophy, with an approximately 50 percent increase in left ventricular mass, was produced by means of perinephritic hypertension. The animals were studied approximately 5 months after the induction of hypertension. Myocardial blood flow to four transmural layers of the left ventricular wall was measured using left atrial injections of 15 μ radioactive microspheres at rest and during two levels of treadmill exercise to increase heart rates to 200 and 260 beats/min, respectively. Mean left ventricular blood flow during resting control conditions was similar in the two groups of dogs. In addition, blood flow increased similarly during exercise so that heart rate or the product of heart rate and systolic blood pressure predicted myocardial blood flow equally well in normal dogs and in those with left ventricular hypertrophy. During resting conditions, subendocardial blood flow significantly exceeded subepicardial blood flow in normal dogs, but exertion abolished this perfusion gradient, resulting in uniform transmural myocardial blood flow during exercise. In contrast, in dogs with left ventricular hypertrophy, blood flow to the subendocardium of the left ventricle significantly exceeded subepicardial blood flow both at rest and during exercise. Nevertheless, this study failed to demonstrate any exercise-induced perfusion deficit within the hypertrophied left ventricle.

Comparative Hemodynamic Effects of Converting Enzyme Inhibitor and Sodium Nitroprusside in Severe Heart Failure

Abstract In nine patients with severe congestive heart failure, the acute response to the infusion of a nonspecific vasodilator, sodium nitroprusside, was compared with the infusion of the converting enzyme inhibitor, teprotide (SQ 20, 881). The hemodynamic effects were similar. Nitroprusside and teprotide increased cardiac index 24 and 20 percent, respectively, reduced mean arterial pressure 11 and 14 percent and pulmonary wedge pressure 21 and 24 percent, and produced no significant change in heart rate (−0.5 and −0.7 percent). Arterial partial pressure of oxygen decreased in response to nitroprusside infusion from 75.8 ± 4.1 to 65.4 ± 3.2 mm Hg (p Therefore, converting enzyme inhibition produces an acute hemodynamic response in severe congestive heart failure comparable with that of sodium nitroprusside with less detrimental acute effect on pulmonary oxygen transport. Long-term oral therapy with converting enzyme inhibitor deserves evaluation in congestive heart failure.

Myocardial blood flow during exercise in dogs with left ventricular hypertrophy produced by aortic banding and perinephritic hypertension.

This study tested the hypothesis that for similar degrees of left ventricular hypertrophy, subendocardial blood flow would be facilitated by the increased diastolic coronary perfusion pressure associated with arterial hypertension, as compared with hypertrophy produced by banding the ascending aorta. Left ventricular hypertrophy was produced with perinephritic hypertension in seven adult dogs and by banding the ascending aorta in nine adult dogs. Left ventricular/body weight ratios were 6.15 +/- 0.59 g/kg in the hypertensive animals and 6.87 +/- 0.47 g/kg in dogs with aortic banding, as compared with 4.23 +/- 0.23 g/kg in seven normal dogs (p less than .01). Studies were performed at rest and during two stages of treadmill exercise to achieve heart rates of 195 and 260 beats/min. Diastolic aortic pressure was increased in animals with hypertension but not in dogs with aortic banding. Systolic ejection period was prolonged in dogs with aortic banding but not in hypertensive dogs. Mean blood flow per gram of myocardium measured with microspheres was similar at rest and during light exercise in all three groups of animals, whereas during heavy exercise blood flow was significantly greater than normal in both groups with hypertrophy. In normal dogs subendocardial/subepicardial (endo/epi) flow ratios did not change significantly during exercise. In both groups with hypertrophy, endo/epi ratios were normal at rest but decreased significantly during exercise. During heavy exercise the endo/epi ratio decreased to 0.73 +/- 0.08 in dogs with aortic banding as compared with 1.07 +/- 0.12 in hypertensive dogs (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)