Increased coronary sinus lactate concentration during pacing induced angina pectoris after clinical improvement by glyceryl trinitrate.

Ten patients with stable angina pectoris and obstructed coronary arteries (greater than 75% reduction in diameter) were studied before and during two periods of pacing, the second of which was preceded by sublingual administration of glyceryl trinitrate (mean dose 0.78 mg). Coronary sinus blood flow measurements and aortocoronary sinus blood sampling for metabolite determinations were carried out. Although the rate of pacing was increased by 10 beats/minute after glyceryl trinitrate administration, the onset of angina was delayed in eight patients during pacing. Drug administration decreased coronary sinus blood flow by 42% and myocardial oxygen uptake by 41% during pacing and induced a shift in mean lactate extraction towards a net release (from 3.1% to -12.6%). It increased the number of patients producing lactate from three to five. Glyceryl trinitrate administration decreased myocardial glucose uptake throughout the study, decreased lactate extraction during recovery, and increased the aortocoronary sinus citrate gradient at rest and during recovery, while the exchange of free fatty acids remained unchanged. A decrease in aortocoronary sinus lactate difference during pacing after glyceryl trinitrate administration correlated positively with the fall in coronary sinus blood flow. The metabolic data do not indicate an augmented myocardial lactate production after glyceryl trinitrate administration. A decrease in coronary sinus blood flow seems, therefore, to be of primary importance in explaining the elevated coronary sinus lactate concentration. Our finding that coronary sinus lactate concentration increased during pacing after glyceryl trinitrate administration despite clinical improvement questions the validity of its use as a quantitative index of ischaemia.     

Myocardial oxygen supply:demand ratio as reference for coronary vasodilatory drug effects in humans.

OBJECTIVE: Introduction and measurement of human myocardial oxygen supply:demand ratio as a reference for quantification of coronary microvascular vasodilating drug effects in clinical studies. Myocardial oxygen consumption is the major determinant of coronary blood flow; therefore, the true vasodilating properties of coronary vasodilating drugs that may have an effect on oxygen consumption cannot be correctly assessed from blood flow changes alone. DESIGN: Prospective, controlled trial. SETTING: Academic hospital. PATIENTS: 12 patients with multivessel coronary artery disease (CAD) undergoing coronary artery bypass grafting. INTERVENTIONS: Cardiac pacing at 30 beats/min above sinus rhythm in awake and anaesthetised patients (fentanyl/pancuronium bromide). MAIN OUTCOME MEASURES: Myocardial oxygen supply, defined as coronary sinus blood flow multiplied by arterial oxygen content; myocardial oxygen demand, defined as coronary sinus blood flow multiplied by arteriovenous oxygen content difference. The change in oxygen demand induced by pacing was related to the change in myocardial oxygen supply in awake and anaesthetised patients. This myocardial oxygen supply:demand ratio determined in the reference study was compared with that induced by intravenous and intracoronary drugs (nifedipine, felodipine, urapidil, and sodium nitroprusside) in two pharmacological studies: patients with CAD undergoing cardiac surgery (45 treated with sodium nitroprusside, 27 with nifedipine, and 27 with urapidil to manage arterial blood pressure); and patients with unstable angina (and a similar degree of CAD) undergoing cardiac catheterisation for diagnostic purposes (10 treated with intracoronary nifedipine and 10 with intracoronary felodipine). RESULTS: When awake, the ratio of pacing induced oxygen supply:demand changes in the 12 reference study patients was 1.50 (95% confidence intervals (CI), 1.41-1.58), similar to the 1.45 (1.35-1.56) measured in the same patients after induction of anaesthesia. Anaesthesia per se did not increase coronary oxygen supply above the expected increase related to demand changes. The only significant change in the oxygen supply:demand ratio was induced by intracoronary bolus administration of nifedipine and felodipine (10.6 (SE 1.9) and 13.9 (1.9) ml/min, respectively, above the demand related supply). CONCLUSIONS: Quantification of coronary vasoactive properties in relation to the physiological reference ratio between myocardial oxygen supply and demand may be a powerful tool to differentiate between true and apparent coronary vasoactive drugs.     

Influence of glyceryl trinitrate and nifedipine on coronary sinus blood flow and global myocardial metabolism during coronary artery operation.

The effects of intravenous infusions of glyceryl trinitrate and nifedipine on systemic haemodynamic function, coronary haemodynamic function, and global myocardial metabolism were compared in two groups of eleven patients with unimpaired left ventricular function undergoing elective coronary artery operation who were anaesthetised with high dose fentanyl. Severe post-sternotomy hypertension developed in three patients in the glyceryl trinitrate group who were resistant to the hypotensive effect of this agent. All patients given nifedipine remained haemodynamically stable. Coronary sinus blood flow and myocardial oxygen consumption increased and coronary vascular resistance decreased after sternotomy in the nifedipine group but not in the glyceryl trinitrate group. There is no satisfactory explanation for the apparently paradoxical increase in myocardial oxygen consumption in the patients given nifedipine. This phenomenon did not appear to be associated with any detrimental effect of left ventricular function. Thus nifedipine was better than glyceryl trinitrate for the control of post-sternotomy hypertension in patients with good left ventricular function. Intravenous nifedipine is not recommended, however, for the intraoperative control of blood pressure in patients with unstable angina or impaired left ventricular function.     

Influence of glyceryl trinitrate and nifedipine on coronary sinus blood flow and global myocardial metabolism during coronary artery operation

The effects of intravenous infusions of glyceryl trinitrate and nifedipine on systemic haemodynamic function, coronary haemodynamic function, and global myocardial metabolism were compared in two groups of eleven patients with unimpaired left ventricular function undergoing elective coronary artery operation who were anaesthetised with high dose fentanyl. Severe post-sternotomy hypertension developed in three patients in the glyceryl trinitrate group who were resistant to the hypotensive effect of this agent. All patients given nifedipine remained haemodynamically stable. Coronary sinus blood flow and myocardial oxygen consumption increased and coronary vascular resistance decreased after sternotomy in the nifedipine group but not in the glyceryl trinitrate group. There is no satisfactory explanation for the apparently paradoxical increase in myocardial oxygen consumption in the patients given nifedipine. This phenomenon did not appear to be associated with any detrimental effect of left ventricular function. Thus nifedipine was better than glyceryl trinitrate for the control of post-sternotomy hypertension in patients with good left ventricular function. Intravenous nifedipine is not recommended, however, for the intraoperative control of blood pressure in patients with unstable angina or impaired left ventricular function.     

Regional distribution of cardiac output at rest and during exercise in patients with exertional angina pectoris before and after nifedipine therapy

The short-term effects of sublingual nifedipine (20 mg) on cardiac output and its distribution at rest and during exercise were evaluated by measurement of iliofemoral blood flow and cardiac output in 10 men with stable angina pectoris controlled by metoprolol. At rest, nifedipine significantly decreased iliofemoral vascular resistance from 294 +/- 36 to 165 +/- 29 dynes.s.cm-5.10(2) (p less than 0.01) and significantly increased iliofemoral blood flow from 0.34 +/- 0.04 to 0.57 +/- 0.11 liters/min (p less than 0.05). Systemic vascular resistance was reduced from 19 +/- 1 to 13 +/- 1 dynes.s.cm-5.10(2) (p less than 0.001) and cardiac output increased significantly from 4.7 +/- 0.3 to 5.8 +/- 0.5 liters/min (p less than 0.05). Mean arterial pressure decreased significantly and heart rate increased significantly. During maximal upright bicycle exercise during nifedipine therapy, iliofemoral vascular resistance and leg blood flow were unchanged compared with control (23 +/- 2 versus 21 +/- 3 dynes.s.cm-5.10(2) and 4.7 +/- 0.5 versus 4.4 +/- 0.6 liters/min), cardiac output remained significantly increased (12.8 +/- 0.8 to 15.2 +/- 1.2 liters/min, p less than 0.05) and systemic vascular resistance remained significantly reduced (8 +/- 1 to 5 +/- 1 dynes.s.cm-5.10(2); p less than 0.001). The proportion of cardiac output distributed to the working lower limbs was significantly reduced at all exercise levels. In summary, nifedipine caused a redistribution of cardiac output by vasodilating nonexercising vascular beds without altering the locally mediated vasodilation in exercising muscle. In patients with coronary artery disease given nifedipine therapy, an increase in exercise tolerance is due to relief of myocardial ischemia rather than to increased peripheral oxygen delivery.     

Acute coronary vasoconstrictive effects of cigarette smoking in coronary heart disease

To investigate the effect of cigarette smoking on the coronary vasculature, coronary sinus flow and myocardial oxygen delivery were measured at rest and during incremental atrial pacing in 10 patients with coronary artery disease. Measurements were then repeated while the patients smoked 2 unfiltered, high-nicotine cigarettes. Although smoking significantly increased the heart rate at rest and double product, coronary sinus flow did not change significantly (141 +/- 32 vs 146 +/- 28 ml/min). At the lowest equivalent pacing rate before and during smoking, the double products were comparable. However, coronary sinus flow was reduced by smoking (146 +/- 28 vs 159 +/- 28 ml/min, p less than 0.01) and coronary vascular resistance was increased (0.96 +/- 0.15 vs 0.83 +/- 0.13 mm Hg ml-1 min, p less than 0.02). The double products were also comparable at the peak pacing rate before and during smoking. Nonetheless, the coronary sinus flow was again lower (167 +/- 23 vs 227 +/- 41 ml/min, p = 0.02) and the coronary vascular resistance was higher (0.77 +/- 0.10 vs 0.63 +/- 0.09 mm Hg ml-1 min, p less than 0.01) during smoking. The transmyocardial arteriovenous oxygen difference was unchanged by smoking; therefore, myocardial oxygen delivery was reduced in proportion to the reductions in coronary sinus flow. Thus, cigarette smoking appears to acutely alter the ability of the coronary vasculature to regulate flow in accordance with the oxygen requirements of the myocardium.     

Effects of altered site of electrical activation on myocardial performance during inotropic stimulation

The effects of altering the site of electrical activation on responses to isoproterenol (ISO) and treadmill exercise were examined in mongrel dogs instrumented for long-term measurement of left ventricular pressure, left ventricular dP/dt, coronary blood flow, cardiac output, left ventricular diameters, and mean arterial pressure and O2 content in the coronary sinus and aorta. During spontaneous rhythm, 0.2 micrograms/kg/min ISO increased heart rate by 90 +/- 7 beats/min, left ventricular dP/dt by 2479 +/- 301 mm Hg/sec, cardiac output by 3.5 +/- 0.9 liters/min, coronary blood flow by 30.4 +/- 3.9 ml/min, and myocardial oxygen consumption (MVO2) by 3.91 +/- 0.84 ml/min. During right atrial pacing at 193 +/- 7 beats/min, the effects of ISO were not different from the effects during spontaneous rhythm, with the exception of a lesser increase in coronary blood flow and lesser reductions in coronary resistance and left ventricular end-diastolic diameter and pressure. During right ventricular pacing at an identical rate, ISO increased left ventricular dP/dt (1140 +/- 158 mm Hg/sec) and cardiac output (2.2 +/- 0.5 liters/min) significantly less (p less than .025) than during either sinus rhythm or right atrial pacing, while MVO2 rose to a higher value. During right ventricular pacing the changes in mean arterial pressure and left ventricular end-diastolic diameters with ISO were not significantly different from those during right atrial pacing. Treadmill exercise induced significantly smaller (p less than .025) increases in left ventricular dP/dt during right ventricular pacing as compared with during either right atrial pacing or sinus rhythm, while MVO2 rose to a higher value.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic and coronary effects of intravenous verapamil in coronary insufficiency

Verapamil inhibits calcium influx through the slow calcium canals. The coronary an haemodynamic effects of intravenous Verapamil were studied in 8 patients with chronic coronary insufficiency documented by coronary arteriography. The following measurements were made in spontaneous rhythm and during atrial pacing under basal conditions and 10 minutes after intravenous Verapamil (0.10 to 0.17 mg/kg) relayed with a continuous infusion of 5 x 10(-3) mg/Kg/mn: heart rate, cardiac output, left ventricularr pressure (Millar 5 F micromanometer), femoral artery pressure, coronary sinus flow by continuous thermodilution, oxygen and lactate concentrations in arterial and arterio-venous oxygen difference, and index of myocardial oxygen consumption and the coefficient of lactate extraction were then calculated. The coronary and haemodynamic effects of atrial pacing were similar before and after Verapamil at a given rate. Left ventricula end diastolic pressure decreased, cardiac output and total systemic resistance were unchanged, dP/dt max increased but to a lesser degree after Verapamil (P less than 0.05). Coronary arterio-venous oxygen difference decreased after Verapamil. The coronary and haemodynamic effects of Verapamil were similar in spontaneous rhythm and during atrial pacing. In spontaneous rhythm, the heart rate and left ventricular end diastolic pressure increased. In spontaneous and paced rhythm, femoral artery pressure, total systemic resistance and dP/dt max decreased. Cardiac output remained the same. Myocardial oxygen consumption decreased mainly because of a reduced coronary arterio-venous oxygen difference and because of unchanged coronary flow in spontaneous rhythm oxygen consumption seems to have a favourable effect on the myocardial energy equilibrium as shown by the increased coefficient of lactate extraction during atrial pacing after Verapamil. This study shows the negative inotropic and arterial vasodilator effects of Verapamil to be responsible for the reduced myocardial oxygen consumption. It also caused coronary artery vasodilation.     

Myocardial metabolic and hemodynamic effects of dichloroacetate in coronary artery disease

Dichloroacetate (DCA), which activates pyruvate dehydrogenase, has the potential to enhance carbohydrate and lactate utilization in animals, but data from patients with coronary artery disease are lacking. Accordingly, 9 patients (ages 49 to 72 years) with angina and coronary artery disease undergoing catheterization were studied. Systemic and coronary hemodynamic and metabolic measurements were made before and during DCA administration (mean dose 35 mg/kg, intravenously). DCA increased left ventricular (LV) stroke volume from 77 +/- 7 to 87 +/- 7 ml and decreased systemic vascular resistance from 1,573 +/- 199 to 1,319 +/- 180 dynes.s.cm-5 (both, p less than 0.01). There were no significant changes in heart rate, mean aortic pressure, LV end-diastolic pressure, LV dP/dt max, coronary sinus flow, coronary resistance or myocardial oxygen consumption, but myocardial efficiency index (LV work/myocardial oxygen consumption) improved from 24 to 32% (p less than 0.05). Myocardial lactate consumption was maintained (21 +/- 8 vs 19 +/- 11 X 10(-3) mEq/min, p is not significant at p less than or equal to 0.05 level) at a lower arterial lactate concentration (0.72 +/- 0.09 to 0.47 +/- 0.08 mEq/liter, p less than 0.05). DCA appears to stimulate myocardial lactate utilization at a lower arterial concentration, cause peripheral vasodilation, augment stroke volume and enhance myocardial efficiency in patients with coronary artery disease.     

Systemic and coronary hemodynamic and neurohumoral effects of levodopa in chronic congestive heart failure

Systemic and neurohumoral effects of oral levodopa were evaluated in 17 patients with severe chronic heart failure. The maximum mean dopamine level achieved after 1.5 g of oral levodopa was 19.6 +/- 16.4 ng/ml. At peak dopamine level, cardiac index increased by 14% from baseline (1.95 +/- 0.55 to 2.27 +/- 0.45 liters/min/m2, p less than 0.05), stroke volume index increased by 14% (22.4 +/- 6.0 to 25.9 +/- 5.8 ml/min/m2, p less than 0.01). There was a trend toward reduced systemic vascular resistance of 13% (1,773 +/- 769 to 1,535 +/- 432 dynes.s.cm-5, p = 0.08). There was no significant change from baseline in heart rate, mean arterial pressure, right atrial pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance and rate-pressure product. In addition, as the arterial dopamine level increased there was a concomitant decrease in plasma norepinephrine level that was sustained for the period of observation. In a subgroup of 8 patients, there was no change in coronary sinus blood flow, myocardial oxygen consumption, myocardial oxygen extraction, lactate extraction and transmyocardial release of catecholamines after levodopa. These findings suggest that oral levodopa, 1.5 g, can improve left ventricular function without adversely affecting myocardial energetics and catecholamine balance.     

Cardiovascular effects of prenalterol on rest and exercise haemodynamics in patients with chronic congestive cardiac failure.

?The cardiovascular effects of the cardioselective beta, agonist prenalterol have been studied in nine patients with severe chronic congestive cardiac failure and in six patients with left ventricular dysfunction resulting from previous myocardial infarction. In the patients with cardiac failure intravenous prenalterol in a dosage of 1.5 microgram/kg bodyweight increased the cardiac index from 1.8 +/- 0.1 to 21.+/- 0.1 1/min per m2 and the left ventricular ejection fraction from 22 +/- 3 to 28 +/- 3%. There was a modest but significant increase in heart rate from 76 +/- 3 to 87 +/- 4 beats/min. Systemic vascular resistance fell from 2285 +/- 51 to 2041 +/- 534 dynes s-1 cm-5. On exercise, the left ventricular filling pressure fell from 33 +/- 6 to 26 +/- 3 and both cardiac index and stroke index increased by 13% and 16%, respectively. There was no significant change in heart rate or systemic blood pressure. In the patients with left ventricular dysfunction, coronary sinus blood flow increased from 107 +/- 11 to 133 +/- 12 ml/min but the increase in myocardial oxygen consumption was small and not significant (11.6 +/- 1.2 and 14.5 +/- 1.9 ml/min). In all patients there was no evidence that prenalterol was arrhythmogenic.     

Alterations in angina threshold with nifedipine during pacing induced angina.

Changes in coronary haemodynamics and angina threshold were determined during atrial pacing in 11 patients with fixed obstructive coronary artery disease with effort angina before and after the administration of 20 mg of oral nifedipine. Coronary vascular resistance decreased at resting and at "subangina" heart rates but not at "angina" rates. Primary coronary vasodilatation with nifedipine was also suggested by higher coronary sinus oxygen content whether at rest or at subangina or angina heart rates. After nifedipine angina occurred at a lower double product and lower myocardial oxygen consumption. These findings suggest that nifedipine is a coronary vasodilator, but angina can occur at a lower angina threshold in some patients with obstructive coronary artery disease.     

Paradoxical fall of tachycardia- and hypoxia-induced coronary flow under conditions of severe coronary stenosis in dogs

It has been stated that the coronary flow paradoxically falls in response to tachycardia if the coronary artery is stenotic and "compliant". To clarify this, we measured coronary vascular resistance by cannulating the left anterior descending coronary artery in open-chest dogs. In constant flow perfusion of 41 +/- 5 ml/min/100 gm, coronary perfusion pressure was decreased by pacing, while at lower flow of 14 +/- 3 ml, it was increased by pacing, indicating that coronary vascular response was reversed. In constant pressure perfusion, coronary vascular resistance was reduced by pacing at high perfusion pressure, while it was paradoxically increased by pacing at low perfusion pressure. In the third experiment at constant flow perfusion, perfusing blood was changed from arterial to venous blood to induce myocardial hypoxia. At high flow, venous blood perfusion reduced coronary vascular resistance, while at low flow it increased coronary vascular resistance. All three experiments indicated that at high perfusion, tachycardia and hypoxia caused a reduction in coronary vascular resistance to meet the increased myocardial oxygen demand; however, at low perfusion, those stimuli increased coronary vascular resistance. The present study showed that the coronary vascular response is reversed at low flow and suggested that those stimuli might reduce flow further in patients with stenotic coronary artery and could be one of the mechanisms causing the development of myocardial infarction in those patients.     

Effects of propranolol on the hemodynamic,coronary sinus blood flow and myocardial metabolic response to atrial pacing

The hemodynamic, coronary sinus blood flow and myocardial metabolic effects of 0.15 mg/kg body weight of intravenously administered propranolol were studied in 19 patients with coronary artery disease and 6 normal patients. Atrial pacing was performed in all patients and produced angina in 15 of the 19 patients with coronary artery disease. In these patients propranolol reduced heart rate from 78 to 69 beats/min, cardiac index from 3.0 to 2.6 liters/min per m² and left ventricular stroke work index from 47 to 43 g-m/m²; it increased total peripheral resistance from 24 to 28 units and lactate extraction from 16.3 to 22.5 percent. There was no significant change in mean arterial pressure, left ventricular end-diastolic pressure, coronary sinus blood flow or myocardial oxygen consumption. During a second pacing stress propranolol produced clinical improvement in 9 of the 15 patients who experienced angina initially. The improvement was associated with less severe abnormalities in S-T depression and left ventricular end-diastolic pressure, increased lactate extraction and no significant change in coronary sinus blood flow or myocardial oxygen consumption. Thus, propranolol appears to be capable of modifying the anginal threshold as determined with atrial pacing, and the clinical response appears to be independent of global changes in coronary sinus blood flow and myocardial oxygen consumption.     

The myocardial oxygen supply/demand ratio in patients with and without coronary artery disease

This study was performed to assess the relationship between coronary sinus blood flow (by thermodilution) and myocardial oxygen demand (heart rate-systolic arterial pressure double product) during atrial pacing in patients with and without coronary artery disease. In 11 individuals with coronary artery disease, pacing was performed to ischemia, as reflected by electrocardiographic changes or lactate production; 8 patients without coronary artery disease served as controls. Coronary sinus blood flow (in ml/min) was similar for the two groups at rest. However, the increase in coronary blood flow from rest to peak pacing was less (P = 0.025) in those with coronary artery disease (50 ± 26 ml/min) than in controls (79 ± 26 ml/min). The ratio of coronary sinus blood flow to double product was the same at rest in both groups (11.1 ± 2.2 × 10^?3 controls, 11.6 ± 2.7 × 10^?3 coronary artery disease; NS). At peak pacing, it was unchanged in the controls (10.4 ± 2.0 × 10^?3) but fell in those with coronary artery disease (9.0 ± 2.5 × 10^?3; P = 0.002). The aortic-coronary sinus oxygen content difference was similar at rest in both groups and did not change in response to pacing in either group. Thus, in response to augmented myocardial oxygen demand, patients without coronary artery disease have an appropriate increase in coronary blood flow and myocardial oxygen supply, while in those with coronary artery disease who develop ischemia the increment in myocardial blood flow (and oxygen supply) is inappropriately low.     

Myocardial metabolism and threshold to angina in coronary artery disease after digitalization: responses at rest and during stress.

To determine the metabolic cost of digitalis to patients with coronary artery disease who were not in congestive heart failure, 15 patients were stressed with atrial pacing before and after the administration of ouabain (0.007 mg/kg). Resting coronary sinus blood flow (118 ± 31 ml/min) and myocardial oxygen consumption (15.8 ± 3.5 ml oxygen/min) increased to 141 ± 25 ml/min (P < 0.05) and 19.8 ± 3.8 ml oxygen/min (P < 0.02) after ouabain administration, but there was no shift to lactate production and no angina. Atrial pacing before and after the infusion of ouabain induced a shift to lactate production (before ouabain: +29 per cent to -3 per cent, P < 0.05; after ouabain: +36 per cent to ?2 per cent, P < 0.01), caused angina in 12 patients (80 per cent) and S-T segment depression in nine patients (60 per cent) whether ouabain was given or not. Furthermore, atrial pacing alone versus atrial pacing plus ouabain produced no significant differences in coronary sinus blood flow (178 ± 63 to 181 ± 90 ml/min) and myocardial oxygen consumption (22.8 ± 6.6 to 23.5 ± 10.1 ml oxygen/min). Yet, 11 of 12 patients (92 per cent) experienced angina within a much shorter period of time after the institution of atrial pacing (152 ± 119 seconds to 46 ± 41 seconds, P < 0.01) if they had previously received ouabain.These findings indicate that digitalization increases myocardial oxygen consumption in nonfailing hearts with coronary artery disease but that this increase is not accompanied by a shift to anaerobic metabolism at rest. Although prior digitalization does not appear to produce additional deleterious metabolic effects during stress, it may sensitize patients to a much earlier awareness of angina.     

Renal hemodynamic effects of vasodilation with nifedipine and hydralazine in patients with heart failure

The central and renal hemodynamic effects of nifedipine were evaluated in nine patients with severe chronic congestive heart failure. Oral nifedipine (34 +/- 22 mg, mean +/- standard deviation) was associated with a decrease in systemic vascular resistance from 1,748 +/- 436 to 1,321 +/- 302 dynes . s . cm-5 (p less than 0.001) and mean arterial blood pressure from 96 +/- 11 to 87 +/- 6 mm Hg (p less than 0.05) and with an increase in cardiac output from 4.2 +/- 1.1 to 4.9 +/- 1.2 liters/min (p less than 0.001). Although renal vascular resistance decreased from 11,988 +/- 2,256 to 10,286 +/- 3,011 dynes . s . cm-5 (p less than 0.05), no significant change was seen in renal blood flow (599 +/- 120 to 640 +/- 162 ml/min), glomerular filtration rate (62 +/- 18 to 62 +/- 17 ml/min), filtration fraction (18 +/- 5 to 17 +/- 6%), the ratio of renal/systemic vascular resistance (7.0 +/- 1.0 to 7.9 +/- 1.8) and the ratio of renal blood flow/cardiac output (0.15 +/- 0.02 to 0.13 +/- 0.03). Intravenous hydralazine (10 +/- 5 mg), given to eight of the patients in a randomized crossover design, resulted in a larger increase in cardiac output than did nifedipine (38 +/- 7 versus 19 +/- 10%, p less than 0.001) and in an increase in total renal blood flow from 570 +/- 152 to 645 +/- 174 ml/min (p less than 0.001). Renal vascular resistance decreased from 12,080 +/- 2,934 to 10,153 +/- 2,372 dynes . s . cm-5 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular effects of prenalterol on rest and exercise haemodynamics in patients with chronic congestive cardiac failure

?The cardiovascular effects of the cardioselective beta, agonist prenalterol have been studied in nine patients with severe chronic congestive cardiac failure and in six patients with left ventricular dysfunction resulting from previous myocardial infarction. In the patients with cardiac failure intravenous prenalterol in a dosage of 1.5 microgram/kg bodyweight increased the cardiac index from 1.8 +/- 0.1 to 21.+/- 0.1 1/min per m2 and the left ventricular ejection fraction from 22 +/- 3 to 28 +/- 3%. There was a modest but significant increase in heart rate from 76 +/- 3 to 87 +/- 4 beats/min. Systemic vascular resistance fell from 2285 +/- 51 to 2041 +/- 534 dynes s-1 cm-5. On exercise, the left ventricular filling pressure fell from 33 +/- 6 to 26 +/- 3 and both cardiac index and stroke index increased by 13% and 16%, respectively. There was no significant change in heart rate or systemic blood pressure. In the patients with left ventricular dysfunction, coronary sinus blood flow increased from 107 +/- 11 to 133 +/- 12 ml/min but the increase in myocardial oxygen consumption was small and not significant (11.6 +/- 1.2 and 14.5 +/- 1.9 ml/min). In all patients there was no evidence that prenalterol was arrhythmogenic.     

Alterations in angina threshold with nifedipine during pacing induced angina

Changes in coronary haemodynamics and angina threshold were determined during atrial pacing in 11 patients with fixed obstructive coronary artery disease with effort angina before and after the administration of 20 mg of oral nifedipine. Coronary vascular resistance decreased at resting and at "subangina" heart rates but not at "angina" rates. Primary coronary vasodilatation with nifedipine was also suggested by higher coronary sinus oxygen content whether at rest or at subangina or angina heart rates. After nifedipine angina occurred at a lower double product and lower myocardial oxygen consumption. These findings suggest that nifedipine is a coronary vasodilator, but angina can occur at a lower angina threshold in some patients with obstructive coronary artery disease.     

Improved myocardial oxygen utilization by diltiazem in patients

Calcium entry blocking drugs produce different effects on systemic and coronary hemodynamics and myocardial oxygen extraction. To examine the effects on myocardial oxygen extraction, intravenous diltiazem (100 micrograms/kg bolus with a continuous 10 micrograms/kg/min infusion) was administered to 11 patients at rest and during controlled heart rates (100 +/- 5 and 120 +/- 5 bpm). At rest, diltiazem decreased mean arterial pressure from 109 +/- 13 to 99 +/- 14 mm Hg (p less than 0.01), increased heart rate from 64 + 12 to 74 +/- 14 bpm (p less than 0.01), and decreased coronary sinus resistance (1.02 +/- .41 to 0.87 +/- .40 U, p less than 0.05). Myocardial oxygen extraction was significantly reduced since coronary sinus oxygen content increased (6.0 +/- 0.9 to 7.8 +/- 1.2 ml/dl, p less than 0.01) and the arterial-coronary sinus oxygen difference decreased (12.0 +/- 1.7 to 10.6 +/- 1.6 ml/dl, p less than 0.01). Similar changes occurred with heart rate held constant. There were no significant changes in absolute coronary sinus blood flow, calculated myocardial oxygen consumption, or left ventricular dP/dt. Diltiazem decreases mean arterial pressure while reducing both myocardial oxygen extraction and coronary arterial resistance, suggesting that a principal mechanism of a beneficial effect upon the coronary circulation appears to be an improvement in myocardial oxygen extraction relative to myocardial oxygen demand.