Effects of Glucose‐Insulin‐Potassium Infusion on QT Dispersion in Patients with Acute Myocardial Infarction

Background: Increased QT dispersion during acute myocardial infarction (AMI) has been associated with the occurrence of ventricular arrhythmias. Also, serum potassium levels have been shown to be relevant to the arrhythmic risk in this group of patients. The aim of the present study was to assess changes in QT dispersion during infusion of glucose‐insulin‐potassium (GIK) during AMI. Methods: Patients from the Pol‐GIK study were analyzed retrospectively. The patients were selected from the placebo (1000 ml of 0.89% NaCI) and the GIK (1000 ml of 10% dextrose, 20–32 units of insulin, 80 mEq K+) groups (18 and 24 patients, respectively). QT interval duration and dispersion the difference between the longest and shortest QT intervals) were measured at baseline, 18–24 hours into placebo/GIK infusion and 24 hours after the end of infusion. Results: In the placebo group, plasma potassium levels changed from 4.1 ± 0.5 mmol/L at baseline to 4.6 ± 0.8 mmol/L during infusion (P < 0.05) and 4.6 ± 0.4 mmol/L after infusion, whereas in the GIK group the respective values were 4.0 ± 0.4, 4.6 ± 0.3 (P < 0.0001), and 4.5 ± 0.5 mmol/L. QT interval duration was stable throughout the study and there was no difference between the groups. The two groups did not differ in respect to QT dispersion at any time point, the respective values were 79 ± 28, 65 ± 25, and 77 ± 27 ms in the placebo group, and 61 ± 35, 60 ± 26, and 76 ± 43 ms in the GIK group. The incidence of arrhythmias was also similar in both groups. Conclusions: GIK, at the dose used, is unlikely to affect heterogeneity of ventricular repolarization during AMI. A.N.E. 2001;6(1)50–54     

Abrupt propranolol withdrawal in angina pectoris: effects on platelet aggregation and exercise tolerance.

Data collected before the initial reports of myocardial infarction following sudden withdrawal of propranolol are presented here to evaluate possible mechanisms for this phenomenon. Twenty patients with angina pectoris were randomized into placebo and propranolol (160 mg./day) treated groups and followed for 50 weeks at which time treatment was abruptly discontinued. Measurements of exercise tolerance, the product of heart rate and blood pressure at exercise end-point (HR × BP), and platelet aggregation thresholds in response to ADP and epinephrine were made before, during, and after treatment. Prior to propranolol, mean total work performance was 765 ± 125 k.p.m., HR × BP (heart rate-blood pressure product) was 16,800 ± 1,535. Mean platelet aggregation threshold with ADP was 1.32 μM¹; with epinephrine 1.26 μM¹. Patients treated with propranolol demonstrated significant improvement in exercise performance (1,790 ± 285 k.p.m., p < .01), reduction in HR × BP (12,000 ± 895, p < .01), and an elevation in platelet aggregation threshold; with ADP 3.43 μM¹ (p < .01); with epinephrine 12.9 μM¹ (p < .01). Following abrupt cessation of propranolol, exercise tolerance and HR × BP fell below pretreatment levels (630 ± 117 k.p.m. and 15,500 ± 513, respectively). Similarly platelet aggregation threshold fell to 1.0 μM¹ with ADP and 0.57 μM¹ with epinephrine. In six patients platelets were significantly more hyperaggregable than prior to therapy. Anginal frequency increased in all, but no acute infarction was observed. Abrupt withdrawal of propranolol may be deleterious in patients, sometimes causing “rebound” platelet hyperaggregability associated with increasing anginal frequency and decreasing exercise tolerance.     

Exercise-related changes in serum catecholamines and potassium: effect of sustained exercise above and below lactate threshold

Plasma potassium and catecholamines exhibit rapid shifts during exercise testing, particularly when exercise intensity exceeds lactate threshold. To assess changes that may occur during sustained exercise, we studied 10 healthy men to determine the effect of 20 minutes of exercise at 25 W above lactate threshold (ALT) and 20 minutes of exercise at 25 W below lactate threshold (BLT). Both conditions showed elevation of catecholamines at end exercise compared to baseline, but catecholamine levels ALT were significantly higher than the levels BLT (2270 +/- 190 versus 900 +/- 230 pg/ml norepinephrine, p less than 0.001; 509 +/- 69 versus 150 +/- 18 pg/ml epinephrine, p less than 0.001). This difference persisted at 2 minutes of recovery (1620 +/- 130 versus 590 +/- 60 pg/ml norepinephrine, p less than 0.001; 216 +/- 31 versus 98 +/- 16 pg/ml epinephrine, p less than 0.001). Both conditions resulted in a significant elevation in potassium at end exercise compared to baseline, but the potassium levels ALT were significantly higher than the levels BLT (1.1 +/- 0.1 mEq/L versus 0.5 +/- 0.1 mEq/L, p less than 0.001. The fall in potassium in the immediate post-exercise period was significantly greater following exercise ALT (-0.8 +/- 0.1 mEq/L versus -0.2 +/- 0.1 mEq/L, p less than 0.001). Thus sustained exercise slightly ALT resulted in a significant potassium flux and very elevated catecholamine levels. Avoiding these metabolic stresses by exercising BLT may decrease chances for exercise-related arrhythmia or other cardiac dysfunction in susceptible patients.     

Exercise responses before and after physical conditioning in patients with severely depressed left ventricular function

The ability of patients with severely impaired left ventricular function to perform short-term exercise and to participate in a cardiac rehabilitation program and attain physical training effects was evaluated. Treadmill exercise tests were performed before and after physical conditioning in 10 patients with a prior myocardial infarction and a left ventricular ejection fraction at rest of less than 27 percent (range 13 to 26) determined by radionuclide angiography. All patients participated in a supervised exercise program with a follow-up period of 4 to 37 (mean 12.7) months. Baseline exercise capacity showed marked variability, ranging from 4.5 to 9.4 (mean 7.0 ± 1.9) METS, and improved to 5.5 to 14 (mean 8.5 ± 2.9) METS after conditioning (p = 0.05). The oxygen pulse (maximal oxygen uptake/maximal heart rate) before and after conditioning was used to assess a training effect and increased significantly from 12.8 ± 2.0 to 15.7 ± 3.2 ml/beat (p < 0.01). There was no exercise-related morbidity or mortality, although two patients died during the study period. It is concluded that selected patients with severely impaired left ventricular function can safely participate in a conditioning program and achieve cardiovascular training effects.     

Echocardiographic LV function in thyrotoxicosis.

Serial echocardiographic studies were made in 11 patients with thyrotoxicosis. In the untreated thyrotoxic state heart rate was increased (96 ± 14 (SD) beats/minute) as were measurements of left ventricular (LV) contractility. LV shortening fraction was 40 ± 6 per cent (mean ± SD), mean velocity of circumferential fiber shortening was 1.60 ± 0.32 circumferences/sec., and velocity of posterior wall motion 71 ± 13 mm./sec. Stroke index and cardiac index were increased: 52 ± 18 (SD) ml./beat per M.² and 5.0 ± 1.8 (SD) liter/minute per M.², respectively. Cardiac chamber size was normal in all but one very ill patient and did not change during the study. Treatment with propranolol, 60 mg./day, produced a dramatic and immediate improvement in the clinical state of the patient. Heart rate decreased to 84 ± 11 beats/minute (p < 0.01), stroke index increased marginally (p > 0.05), and cardiac index was unaltered (p > 0.05). There was no change in parameters of LV contractility (p > 0.05). Treatment with a specific antithyroid drug (methimazole or propylthiouracil) brought about further improvement in the clinical state and a further decrease in heart rate (p < 0.01). LV contractility decreased and after two to three months, when the patients were euthyroid, these measurements were in the range of normal (per cent shortening of the LV diameter 37 ± 4, p < 0.01; mean velocity of circumferential fiber shortening 1.31 ± 0.23 circumferences/sec., p < 0.05; maximum velocity of posterior wall motion, 46 ± 14 mm./sec., p < 0.01). Systolic time interval measurements were in keeping with these data. They showed enhanced LV performance in the control state, no change with propranolol, and they returned toward the range of normal after definitive antithyroid treatment.     

Influence of verapamil therapy on left ventricular performance at rest and during exercise in hypertrophic cardiomyopathy

To determine the hemodynamic effect of verapamil at rest and during exercise, 18 patients with hypertrophic cardiomyopathy were studied before and after 7 weeks of treatment with oral verapamil (maximal dose, 720 mg/day). At rest and at peak exercise, verapamil produced a significant increase in left ventricular (LV) systolic performance in terms of stroke volume index (rest, from 43 ± 11 to 53 ± 11 ml/m², p < 0.001; exercise, from 46 ± 11 to 51 ± 10 ml/m², p < 0.01), whereas heart rate decreased (rest, from 81 ± 14 to 70 ± 11 min^?1, p < 0.001; exercise, from 150 ± 21 to 141 ± 18 min^?1, p < 0.01). Cardiac index at rest and during exercise remained unchanged. Systolic vascular resistance did not change at rest, but decreased significantly during exercise (974 ± 243 to 874 ± 174 dynes s cm^?5; p < 0.05). After verapamil administration, pulmonary artery pressures did not change at rest, but decreased significantly during exercise. This was probably due to a shift in the LV pressure-volume relation. The improvement in LV hemodynamics was associated with a significant increase in exercise capacity. The findings of this study indicate that in patients with hypertrophic cardiomyopathy, hemodynamic improvement at rest and during exercise can be achieved by chronic administration of verapamil.     

Effects of isosorbide dinitrate and hydralazine on regional metabolic responses to arm exercise in patients with heart failure

The reduced exercise capacity of patients with heart failure is thought to be due in part to impaired skeletal muscle oxygen delivery. To determine if hydralazine and isosorbide dinitrate improve skeletal muscle oxygen delivery in such patients, the effects of these agents on regional metabolic responses to forearm exercise were examined in 16 patients with heart failure. Arm oxygen extraction and brachial venous lactate concentration were measured at rest and during 3 minutes of rhythmic handgrip and then remeasured after administration of oral hydralazine (nine patients) or sublingual isosorbide dinitrate (nine patients). Hydralazine increased mean (± standard deviation) cardiac output at rest from 3.5 ± 0.5 to 4.9 ±1.0 liters/min (p < 0.01) and decreased arm oxygen extraction from 39 ± 8 to 33 ± 10 percent (probability [p] < 0.01), suggesting improved resting limb oxygen delivery. However, hydralazine did not reduce arm oxygen extraction during exercise (control 63 ± 4, hydralazine 60 ± 12 percent; p = notsignificant[NS]) or venous lactate during exercise (control 16.6 ± 7.8, hydralazine 17.1 ± 4.8 mg/100 ml; p = NS). Isosorbide dinitrate increased the cardiac output from 3.6 ± 0.7 to 4.5 ± 0.7 liters/min (p < 0.01) but had no effect on arm oxygen extraction at rest (control 40 ± 11, isosorbide dinitrate 38 ± 11 percent; p = NS) and during exercise (control 66 ± 5, isosorbide dinitrate 64 ± 8 percent; p = NS) or on venous lactate during exercise (control 17.9 ± 6.4, isosorbide dinitrate 17.1 ± 3.9 mg/100 ml; p = NS). These data suggest that hydralazine and isosorbide dinitrate do not improve skeletal muscle oxygen delivery during exercise in patients with heart failure.     

Circulatory improvement after hydralazine or isosorbide dinitrate administration in patients with heart failure: Effect on metabolic responses to submaximal exercise

Hydralazine and isosorbide dinitrate can increase the cardiac output during submaximal exercise in patients with heart failure but whether this increase improves oxygen delivery to underperfused exercising muscle is uncertain. To investigate this question, we measured three systemic markers of skeletal muscle oxygen availability—exercise V?O₂, mixed venous lactate concentration and oxygen debt—during submaximal exercise in 15 patients with heart failure both before and after hydralazine (nine patients) or isosorbide dinitrate (eight patients) administration. Hydralazine increased the cardiac output during exercise from 4.9 ± 1.2 liter/min to 6.5 ± 1.8 liter/min (p < 0.01) but had no effect on exercise V?O₂ (control, 531 ± 135 ml/min; hydralazine, 489 ± 102 ml/min), peak lactate concentration (control, 18.3 ± 4.2 mg/dl; hydralazine, 17.9 ± 3.6 mg/dl) or oxygen debt (control, 474 ± 213 ml; hydralazine, 465 ± 170 ml) (all p > 0.10). Isosorbide dinitrate increased the cardiac output during exercise from 4.6 ± 0.9 liter/min to 5.3 ± 0.8 liter/min (p < 0.01) but also did not change exercise V?O₂ (control, 488 ± 62 ml/min; isosorbide, 473 ± 44 ml/min), peak lactate concentration (control, 19.2 ± 6.0 mg/dl; isosorbide, 21.4 ± 8.2 mg/dl) or oxygen debt (control, 522 ± 154 ml; isosorbide, 445 ± 147 ml) (all p > 0.10). We conclude that short-term administration of hydralazine or nitrates to patients with heart failure can substantially improve circulatory function during exercise but that this improvement probably does not enhance skeletal muscle nutritional flow.     

Postextrasystolic aortic pressure pulse response in coronary artery disease.

The response of the aortic systolic pressure after an extrasystole was evaluated in 100 consecutive patients with coronary artery disease. The patients were divided into four groups depending on the response of the first postextrasystolic beat. Group IA (45 patients), had lower systolic pressure, whereas group IB (40 patients), had a similar systolic pressure in the postextrasystolic beat, as compared to beats preceding the extrasystole. Group IIA (12 patients) and group IIB (3 patients), demonstrated an increased systolic pressure in the first postextrasystolic beat with subsequent beats in group IIB, also demonstrating pulsus alternans. Congestive heart failure and cardiomegaly were significantly more frequent in group II, as compared to group I patients. In group IIA and IIB, triple vessel disease was present in 83 and 100 per cent, respectively, as compared to 44 per cent in group I patients. Left ventricular end-diastolic pressure (mm. Hg) was 14 ± 6 and 12 ± 7 in group IA and IB respectively, as compared to 19 ± 9 (p < 0.025) in group IIA and 31 in group IIB. Comparing groups IA and IB with each other for cardiac output, stroke volume, end-diastolic volume and ejection fraction, revealed no significant difference. The cardiac output (L./min./M.²) was 2.2 ± 0.6 for group IIA, as compared (p < 0.01) to 2.8 ± 0.5 and 2.9 ± 0.5 in groups IA and IB. Stroke volume (ml./M.²) and ejection fraction were 30 ± 10 and 0.30 ± 0.08, respectively, for group IIA, which is signficantly less, as compared to group I patients. The end-diastolic volume (ml./M.²) in group IIA was 102 ± 28, which is significantly (p < 0.001) higher, as compared to group IA and IB. All patients in group IIB had an abnormal cardiac output, end-diastolic volume and ejection fraction. Thus, the differences in response between group I and group II patients to an extrasystole clearly define two distinct hemodynamic groups. The responses observed to an extrasystole are best explained by variable response of each group to postextrasystolic potentiation and aortic impedance.     

Enhancement of left ventricular function by glucose-insulin-potassium infusion in acute myocardial infarction

Twenty-eight patients admitted to the hospital with suspected acute myocardial infarction underwent baseline studies within 12 hours of onset of symptoms. Patients were then randomized to receive control infusion (0.45 percent sodium chloride at 20 ml/hour) (15 patients) or glucoseinsulin-potassium infusion (300 g glucose, 50 units regular insulin, 80 mEq KCl/liter water at 1.5 ml/kg per hour) (13 patients) for 48 hours. All patients received 0.45 percent sodium chloride for 2 more days. Coronary arteriograms and left ventriculograms were obtained in 26 (93 percent) of 28 patients 2 to 3 weeks after infarction.Radionuclide ejection fraction improved during glucose-insulin-potassium infusion (49 ± 4 to 55 ± 5 percent, p < 0.01). Before discharge, the angiographic ejection fraction was greater in the glucose-insulin-potassium recipients than in control patients (43 ± 3 versus 35 ± 3 percent, p < 0.05). Radionuclide ejection fraction decreased in all control patients during the study (42 ± 4 to 37 ± 3 percent, p < 0.0005) and did not change significantly in the treated group (49 ± 4 to 43 ± 5 percent, p = not significant [NS] by paired t test). Regional wall motion analysis revealed an increase in ejection fraction in the “infarcted zone” in the treated group only (44 ± 7 to 54 ± 8 percent, p < 0.01) during glucose-insulin-potassium infusion. There was also a significant decrease in ejection fraction in the “noninfarcted zone” in the control group only (50 ± 4 to 45 ± 4 percent, p < 0.01).During experimental infusion pulmonary arterial end-diastolic pressure decreased in the glucose-insulin-potassium group (17 ± 2 to 12 ± 2 mm Hg, p < 0.01) without changing significantly in the control group. Calculated end-diastolic and end-systolic volume indexes changed in opposite directions in the two groups during experimental infusion (end-diastolic volume index 80 ± 5 to 90 ± 9 ml/m² in the control group versus 70 ± 9 to 55 ± 6 ml/m² in the treated group, p < 0.005 for change from baseline value between groups and the end-systolic volume index 48 ± 6 to 55 ± 8 ml/m² in the control group versus 39 ± 8 to 26 ± 5 ml/m² in the treated group (p < 0.01 for change from baseline value between groups).These data suggest that glucose-insulin-potassium infusion after acute myocardial infarction in human beings (1) increases global ejection fraction, (2) Increases ejection fraction in the “infarcted zone” without changing ejection fraction in the “noninfarcted zone”, and (3) decreases pulmonary arterial end-diastolic pressure and end-diastolic and end-systolic volumes.     

Effect of nitrates on left ventricular size and function during exercise: Comparison of sublingual nitroglycerin and nitroglycerin paste

To compare the effects of sublingual nitroglycerin and nitroglycerin paste on left ventricular size and performance during supine bicycle exercise, equilibrium radionuclide angiography was performed in 36 persons classified into two groups of normal subjects and two groups of patients with angiographically proved coronary heart disease. Each group underwent a control exercise study, and then one group of normal subjects and one group of patients were restudied after the administration of 0.6 mg of nitroglycerin or 2 inches (5 cm) of nitroglycerin paste (but not both). Data were collected at rest and at peak exercise.In normal subjects exercise resulted in increased ejection fraction, decreased end-systolic volume and little change in end-diastolic volume. After either drug, volumes at rest markedly decreased, and during exercise, ejection fraction increased to levels comparable with pre-drug levels. After nitroglycerin paste the reduction in volume seen at rest persisted during exercise, but after sublingual nitroglycerin end-diastolic volume increased during exercise (88 ± 43 to 113 ± 30 ml [mean ± standard deviation]; p < 0.01). Peak exercise end-diastolic volume after nitroglycerin was still lower than that before nitroglycerin (113 ± 30 versus 120 ± 28 ml, p < 0.05).In patients with coronary disease, ejection fraction did not change during exercise, but both end-diastolic and end-systolic volumes increased. After either drug ejection fraction at rest was unchanged, although ventricular volumes were markedly lower (p < 0.05). Ejection fraction increased with exercise in both groups with coronary disease after either drug. After sublingual nitroglycerin, volumes increased during exercise although the peak exercise end-diastolic volume was still lower than the control value (113 ± 31 versus 145 ± 34 ml; p < 0.01). After paste administration, end-diastolic volume did not change during exercise, and end-systolic volume decreased (41 ± 20 to 36 ± 22 ml; p < 0.05).Thus, sublingual nitroglycerin and nitroglycerin paste improved left ventricular function during exercise. The effect of paste on end-diastolic volume appeared sustained, whereas that of sublingual nitroglycerin was transient, confirming the hypothesis that reduction in end-diastolic volume and, by implication, left ventricular wall tension, is a major mechanism of nitrate action.     

Effects of acute and chronic minoxidil administration on rest and exercise hemodynamics and clinical status in patients with severe,chronic heart failure

The effects of acute and chronic oral administration of the vasodilator minoxidil on hemodynamics, oxygen consumption, exercise performance and clinical status were investigated in 10 patients with severe, chronic heart failure refractory to digitalis and diuretic therapy. The cardiac index was 1.99 ±0.38 liters/min/m² at rest and 2.88 ± 0.79 at symptom-limited maximal exercise on conventional therapy, compared with 2.64 ± 0.33 liters/min/m² at rest and 3.55 ± 0.84 at maximal exercise after short-term minoxidil administration (p < 0.02, control versus minoxidil at both rest and exercise). Stroke volume was increased after minoxidil treatment, without significant effect on heart rate. Systemic vascular resistance was decreased by minoxidil from 2,050 ± 722 to 1,325 ± 374 dynes-s/cm^?5 at rest and from 1,500 ± 830 to 1,206 ± 589 dynes· s/cm^?5 at maximal exercise (p = 0.01, control versus minoxidil). No significant effect was observed on left ventricular filling, right atrial, or mean pulmonary arterial pressure, but pulmonary vascular resistance decreased both at rest and on exercise (p < 0.05). Maximal exercise oxygen consumption increased from 8.9 ± 3.2 ml/kg/min on conventional therapy to 10.5 ± 2.4 on minoxidil therapy (p < 0.03), median maximal exercise work load increased from 25 to 50 W and median exercise duration increased from 6.0 to 9.0 minutes. On chronic minoxidil administration all 5 patients who completed a scheduled 6 week follow-up showed symptomatic improvement. However, worsening edema developed in all patients, requiring increased diuretic dosage and close supervision. Symptoms of ischemic heart disease worsened in 2 of 10 patients. We tentatively conclude that minoxidil may be a useful vasoactive agent in the pharmacologic therapy of severe chronic heart failure.     

Comparative influence of ouabain,norepinephrine and heart rate on myocardial oxygen consumption and inotropic state in dogs

The purpose of this study was to compare the myocardial oxygen cost of augmented inotropic state produced by ouabain, norepinephrine, or increased heart rate. This problem was examined in dogs using an isovolumically contracting left ventricular preparation. Inotropic state was measured as the maximum observed contractile element velocity at the lowest common level of wall stress (MAX V). Peak left ventricular wall stress was maintained constant in each dog so that it would not influence changes in myocardial oxygen consumption (MVO₂). Ouabain (4 × 10² μmoles/Kg.) and norepinephrine (2 × 10³ μmoles/Kg./minute) always augmented inotropic state (MAX V) and increased MVO₂. The positive slopes of the regression of MVO₂ on MAX V for ouabain (45.4 ± 12.5 μl/beat/100 Gm./muscle length/sec; mean ± SEM) and norepinephrine (34.5 ± 5.6 μl/beat/100 Gm./muscle length/sec; mean ± SEM) were not significantly different, indicating that for an equal augmentation of inotropic state, ouabain increases myocardial oxygen demands to the same extent as does norepinephrine. When the results with ouabain or norepinephrine were compared to results obtained by altering heart rate, it was found that increasing inotropic state by these pharmacologic agents is more costly in terms of myocardial energy demands than when inotropic state is enhanced by increasing heart rate.     

Follow-up of 91 living-related renal allograft donors

The long-term risks of uninephrectomy in the living-related kidney donors are of concern. We studied the outcome in living-related allograft donors after donation who have been followed up at Princess Margaret Hospital from 1980 to 1996 by comparing renal function, blood pressure and proteinuria.Ninety-one allograft donors, aged from 19 to 59 years (mean 36.61 ±7.63 years; 43 males and 48 females) were followed up for 1 to 17 years (mean 5.5 ±2.5 years). After nephrectomy, serum creatinine rose by 46.2% from baseline 81.3 ±13.0 μmol/L to 118.9 ±32.9 μmol/L at 3 months (p < 0.001). In 58 of the 91 patients who were followed up for more than 3 years, serum creatinine decreased to 99.7 ±13.2 μmol/L (p < 0.05) at the end of the study period as compared with serum creatinine at 3-month follow-up. Creatinine clearance also decreased from 107.6 ±24.0 ml/min before nephrectomy to 78.8 ±15.7 ml/min at 1-year follow-up (p < 0.001). Then it became 79.8 ±18.3 ml/min at the latest follow-up (p = 0.599). Systolic blood pressure increased from 114.2 ±8.6 mmHg before nephrectomy to 120.0 ±10.4 mmHg (p < 0.001) at the latest follow-up after nephrectomy. Meanwhile, the diastolic blood pressure rose from 71.1 ±7.2 mmHg at baseline to 73.1 ±8.3 mmHg at the end of the study period (p = 0.091). The mean arterial blood pressure increased from 85.5 ±7.0 mmHg to 88.7 ±8.1 mmHg at the latest follow-up (p > 0.005). Proteinuria increased from 65 ±55 mg/day to 96 ±55 mg/day at the latest follow-up (p = 0.142).In conclusion, there was no progression of renal dysfunction in renal allograft donor after nephrectomy. Serum creatinine even improved significantly at the end of the study period as compared with that at 3-month postnephrectomy. Systolic blood pressure and mean arterial blood pressure had a small increment at the latest follow-up. The prevalence of hypertension was 4.4%. Moreover, proteinuria did not show a significant increase after donation.     

Favorable effects of hydralazine on the hemodynamic response to isometric exercise in chronic severe aortic regurgitation

The hemodynamic effects of isometric exercise and the response to hydralazine therapy were evaluated in 11 patients with chronic, severe aortic regurgitation (AR). Isometric exercise produced a significant increase in heart rate (from 78 ± 11 to 93 ± 19 beats/min [mean ± standard deviation], p < 0.05), mean blood pressure (from 83 ± 8 to 104 ± 20 mm Hg, p < 0.05), mean right atrial pressure (from 3 ± 2 to 7 ± 5 mm Hg, p < 0.05) and mean pulmonary artery wedge pressure (from 12 ± 7 to 18 ± 10 mm Hg, p < 0.05). Small and insignificant changes were seen in cardiac index (from 3.4 ± 0.8 to 3.9 ± 1.0 liters/min/m²), systemic vascular resistance (from 1,097 ± 257 to 1,171 ± 284 dynes s cm^?5), pulmonary vascular resistance (from 120 ± 76 to 130 ± 89 dynes s cm^?5) and stroke volume index (from 44 ± 10 to 43 ± 12 ml/m²). After oral hydralazine administration (100 to 300 mg), hemodynamic values during isometric exercise were: Heart rate increased further, to 105 ± 14 beats/min (p < 0.05), mean blood pressure was 102 ± 16 mm Hg (difference not significant [NS]) cardiac index increased markedly, to 5.2 ± 1.4 liters/min/m² (p < 0.05), stroke volume index increased to 49 ± 12 ml/m² (p < 0.05), right atrial pressure decreased slightly, to 5 ± 5 mm Hg (NS), pulmonary artery wedge pressure decreased to 14 ± 7 mm Hg (p < 0.05), systemic vascular resistance decreased to 903 ± 288 dynes s cm^?5 (p < 0.05), and pulmonary vascular resistance changed to 100 ± 66 dynes s crrr^?5 (NS). Thus, isometric exercise in patients with chronic severe AR is associated with only a slight and insignificant increase in systemic vascular resistance, but a marked increase in pulmonary artery wedge pressure. Direct arteriolar vasodilation with hydralazine results in a significant attenuation of pulmonary artery wedge pressure increase during isometric exercise and leads concomitantly to a significant augmentation of stroke volume and cardiac output. These findings substantiate the value of hydralazine therapy in patients with chronic, severe AR.     

Radionuclide assessment of ventricular performance during propranolol withdrawal prior to aortocoronary bypass surgery

The effects of oral propranolol upon left ventricular performance were assessed in 18 patients with angiographically documented coronary artery disease in whom propranolol was tapered prior to elective aortocoronary bypass surgery. Left ventricular ejection fraction, ejection rate, and regional wall motion were obtained on three occasions with first-pass radionuclide angiocardiographic techniques. Patients were studied at peak propranolol dose (±SEM) 224±29 mg./day; serum propranolol level, 85±22 ng./ml.), intermediate dose (99±9 mg./day; serum propranolol, 30±6 ng./ml.), and 24 hours following discontinuation of propranolol therapy.Heart rate increased significantly (62±2.3 vs 67±3.0 vs 73±2.3 beats/minute, p<0.001) during propranolol withdrawal, while systolic blood pressure did not change significantly (114.7±4.3 vs 110.3±3.0 vs 113±3.0 mm. Hg, p>0.05). There was no significant change in ejection fraction (59.1±2.4 vs 60.4±2.0 vs 59.2±2.5 per cent) or ejection rate 2.80±0.18 vs 2.87±0.18 vs 2.92±0.20 sec.^?1) as propranolol was tapered (p>0.05). No patient demonstrated a change in regional wall motion in response to propranolol withdrawal. The results of this study suggest that oral proparanolol in commonly used clinical dosages does not significantly affect radionuclide measures of left ventricular performance in the basal state.     

A role for endogenous prostaglandins in defective glucose potentiation of nonglucose insulin secretagogues in diabetics

Noninsulin dependent diabetics have insulin responses to nonglucose secretagogues that are subnormal for their plasma glucose levels. Since endogenous prostaglandins have been implicated in the abnormal insulin responses to glucose in diabetics, the present study was performed to explore whether prostaglandins might also play a role in the defective insulin responses to nonglucose stimuli. We examined the effects of infusions of either prostaglandin E₂ (PGE₂) or sodium salicylate (SS), a PG synthesis inhibitor, on the acute insulin responses (AIR's) to arginine and isoproterenol and on the glucose potentiation of the insulin response to arginine in both normal and diabetic subjects. The AIR to arginine was augmented by SS in diabetics (SS = 61 ± 12 μU/ml, control = 37 ± 5 μU/ml, n = 11, p < .01). SS, however, had no effect on the AIR to arginine in normal subjects (SS = 39 ± 4 μU/ml, control = 34 ± 4 μU/ml, n = 6, p = ns). Similarly, SS augmented the AIR to an isoproterenol pulse in diabetics (SS = 38 ± 9 μU/ml, control = 18 ± 3, n = 9, p < .05) but not in normal subjects (SS = 19 ± 4 μU/ml, control = 21 ± 4 μU/ml, n = 8, p = ns), suggesting a SS-sensitive defect in the insulin response to these nonglucose stimuli in diabetics. Conversely, PGE₂ inhibited the AIR to arginine in diabetics (PGE = 28 ± 5 μU/ml, control = 39 ± 7 μU/ml, n = 7, p < .05), but not in normal subjects (PGE = 74 ± 7 μU/ml, control = 80 ± 14 μU/ml, n = 5, p = ns). The effect of SS on glucose potentiation of the AIR to arginine was studied by measuring the AIR to arginine at two different levels of plasma glucose, one before and one after an insulin infusion, with glucose potentiation defined as the ratio ΔAIR/Δprestimulus glucose. Glucose potentiation was significantly less in diabetics than in normals and SS significantly improved glucose potentiation toward normal values in diabetics but did not change glucose potentiation in normals. These findings suggest that endogenous PG's may play a role in the defective glucose potentiation of the AIR to nonglucose secretagogues in diabetics resulting in impaired insulin responses to these stimuli. This defect is partially reversible by an inhibitor of PG synthesis.     

Effects of disopyramide on left ventricular function: Assessment by radionuclide cineangiography

To determine the effects of disopyramide on resting systolic left ventricular (LV) function and LV functional reserve, gated equilibrium radionuclide cineangiography was performed at rest and during maximal symptom-limited supine bicycle exercise in 12 patients after a single 300 mg oral loading dose of disopyramide, and in 22 patients (including the 12 patients just mentioned) after they received disopyramide 150 mg 4 times daily for 5 to 10 days (average 7). The oral loading dose (average serum level 3.6 ± 1.3 μg/ml [standard deviation]) produced decreases in ejection fraction in 9 of 12 patients with a decrease in average resting ejection fraction from 40 ± 15% to 33 ± 11% (p <0.005). However, the lower, sustained dosage of disopyramide was associated with a lower average serum level of 2.5 ± 0.8 μg/ml and with smaller but significant decreases in ejection fraction in 3 of 22 patients during exercise only. At this dosage there was no significant decrease in average ejection fraction for the group at rest or during exercise. Adverse effects of disopyramide on ejection fraction occurred even in patients with previously normal LV function at rest. Hence, disopyramide may be associated with significant decreases in LV systolic function, particularly when given in high, oral “loading” doses. However, sustained therapy with lower dosages as well as lower drug levels is also associated with less depression of LV function.     

Cardiac effects of prolonged and intense exercise training in patients with coronary artery disease

The effects of intense and prolonged exercise training on the heart were studied with echocardiography in eight men with coronary artery disease with a mean age ( ±standard error of the mean) of 52 ± 3 years. Training consisted of endurance exercise 3 times/week at 50 to 60 percent of the measured maximal oxygen uptake for 3 months followed by exercise 4 to 5 days/week at 70 to 80 percent of maximal oxygen uptake for 9 months. Maximal oxygen uptake capacity increased by 42 percent (26 ± 1 versus 37 ± 2 ml/kg per min; p < 0.001). Heart rate at rest and sub-maximal heart rate and systolic blood pressure at a given work rate were significantly lower after training. Systolic blood pressure at the time of maximal exercise increased (145 ± 9 before versus 166 ± 8 mm Hg after training; probability [p] < 0.01). Left ventricular end-diastolic diameter was increased after 12 months of training (from 47 ± 1 to 51 ± 1 mm; p < 0.01). Left ventricular fractional shortening and mean velocity of circumferential shortening decreased progressively in response to graded isometric handgrip exercise before training but not after training. At comparable levels of blood pressure during static exercise, mean velocity of circumferential shortening was significantly higher after training (0.76 ± 0.04 versus 0.98 ± 0.07 diameter/sec, p < 0.01). No improvement in echocardiographic or exercise variables was observed over a 12 month period in another group of five patients who did not exercise. Thus the data suggest that prolonged and vigorous exercise training in selected patients with coronary artery disease can elicit cardiac adaptations.     

Differential effects of Renografin-76 on the ischemic and nonischemic myocardium

The effects of intracoronary diatrizoate meglumine and diatrizoate sodium (Renografin-76) on regional contraction were examined in the normal coronary circulation and during partial (50 percent) coronary occlusion in 11 dogs using strain and length gauges. Intracoronary injections of Renografin-76 (1.5 cc) (1,690 mosM/liter; 0.19 mEq Na/ml), equiosmolar dextrose solution and 0.19 mEq Na⁺/ml saline solution were made randomly. Renografin-76 caused a decrease in preejection tension to 87.4 ± 4.3 percent (p < 0.025), total tension to 74.6 ± 3.3 percent (p < 0.01) and ejection tension to 11.9 ± 12.6 percent (p < 0.001) of control value. Segment length increased to 106.7 ± 7.3 percent of control value. These changes lasted only 12 ± 2 (range 5 to 20) seconds (mean ± standard error of the mean). During partial coronary occlusion and after injection of Renografin-76, preejection tension decreased from 91.7 ± 6.3 to 53.8 ± 3.9 percent (p < 0.01), total tension from 89.9 ± 5.0 to 59.7 ± 3.5 percent (p < 0.01) and ejection tension from 22.8 ± 8.1 to 17.8 ± 10.9 percent, whereas segment length increased from 112.7 ± 3.7 to 130.7 ± 4.6 percent (p < 0.01) of control value. In contrast to findings in the normal coronary circulation, tension and length changes lasted 54 ± 16 (range 15 to 180) seconds (p < 0.05). The hyperemic response during normal coronary circulation was completely abolished during partial coronary occlusion. Prior administration of nitroglycerin did not shorten the duration of the myocardial depressant effects of Renografin. Injections of equiosmolar dextrose or saline solution produced qualitatively similar but quantitatively less marked changes. Thus, intracoronary Renografin-76 has an accentuated and prolonged depressant effect on the ischemic as compared with the normally perfused myocardium; this effect is not solely due to its hyperosmolarity or sodium concentration.