Systemic and coronary hemodynamic effects of combined intravenous diltiazem and nitroglycerin administration

This study evaluated left ventricular (LV) and coronary hemodynamic effects of intravenous nitroglycerin (NTG) in the presence of an intravenous infusion of diltiazem in 15 patients with severe coronary disease. Diltiazem (250 microgram/kg bolus followed by 1.4 micrograms/kg/min infusion) alone decreased mean systemic blood pressure (mean 6%) without changing heart rate or LV end-diastolic pressure. The rate of rise in LV pressure declined slightly (4%), and peripheral resistance decreased (19%). Coronary sinus (CS) and great cardiac vein (GCV) flows were preserved. Addition of NTG (average, 68 micrograms/min) decreased systemic pressure further (7%) as LV end-diastolic pressure declined (5 mm Hg). These pressure changes were accompanied by a 10% increase in heart rate (compared with the heart rate found with diltiazem alone). Peripheral resistance was similar to values after diltiazem alone. The CS and GCV flows did not decrease. The sequence of intravenous drug administration was reversed in three other patients with combination therapy, producing similar effects, regardless of which drug was administered first. Hemodynamic effects of intravenous diltiazem alone and its combination with intravenous NTG seemed potentially favorable for patients with ischemic heart disease.     

Systemic, left ventricular and coronary hemodynamic effects of intravenous diltiazem in coronary artery disease

Systemic and coronary hemodynamic effects of intravenous diltiazem, administered as a bolus of 250 micrograms/kg followed by an infusion of 1.4 micrograms/kg/min, were examined in 14 patients with effort angina. There was no change in heart rate despite significant decreases in systolic, diastolic and mean systemic pressures (13%, 10% and 11%, respectively, all p less than 0.01). The blood pressure decrease was closely correlated with the initial blood pressure (r = 0.81, p less than 0.05). Neither left ventricular end-diastolic pressure nor peak dP/dt changed significantly, but peripheral vascular resistance decreased 16% (p less than 0.001) and stroke volume index increased 10% (p less than 0.05). The pressure-rate product decreased 15% (p less than 0.005), but coronary blood flow was maintained as coronary resistance decreased 14% (p less than 0.025). Diltiazem increased regional coronary flow in some patients. Thus, intravenous diltiazem dilates coronary and systemic resistance vessels, without an increase in heart rate, favorably altering indexes of myocardial oxygen supply and demand.     

Kinetics and hemodynamic effects of intravenous nicardipine modified by previous propranolol oral treatment

Summary Intravenous nicardipine, 5 mg, was administered in two comparable groups of eight patients with chronic coronary artery disease but no clinical signs of heart failure. One group had received no previous treatment and served as a control group, and the other had received long-term treatment with large oral doses of propranolol. Blood concentrations of nicardipine were higher, and the area under the plasma concentration curve was greater in the group previously treated by propranolol. The total clearance of nicardipine was decreased in patients taking propranolol, without a change in the half-life of the drug. Typical hemodynamic responses, namely, a decrease in aortic pressure and in arterial resistances, were greater and more lasting in patients previously treated orally by propranolol. Filling pressure remained stable in both groups. The nicardipine infusion did not induce signs of dromotropic or inotropic negative effects in either group. The greater and more lasting hemodynamic effects of nicardipine in the group previously treated orally by propranolol do not seem to be related to an overall hemodynamic action of propranolol, but are probably due to higher nicardipine plasma levels, and may be caused by a decrease in hepatic blood flow induced by propranolol, with a consequent decrease in nicardipine clearance and by a smaller nicardipine volume of distribution in the propranolol group.     

Acute hemodynamic effects of intravenous nicardipine in patients treated chronically with propranolol for coronary artery disease

Intravenous nicardipine, 5 mg, was infused over 5 minutes in 2 comparable groups of 8 patients with chronic coronary artery disease but no clinical signs of heart failure. Eight patients had received no previous treatment and served as a control group; 8 other patients had received long-term treatment with large doses of propranolol. The hemodynamic responses to nifedipine were similar in the 2 groups, but was greater in patients taking propranolol. At 10 minutes, systemic vascular resistance decreased by 47% in patients taking propranolol and by 39% in the control group; mean aortic pressures decreased by 25% and 10%; heart rate increased by 23% and 19%; and cardiac index increased by 45% in both groups. At 20 minutes, left ventricular end-systolic volume index decreased by 20% in patients taking propranolol and 15% in the control patients; angiographic stroke index increased by 19% and 8%; left ventricular ejection fraction increased by 22% and 11%; and mean circumferential fiber velocity increased by 46% and 32%. Intravenous nicardipine infusion (5 mg) did not induce negative inotropic effects in patients with chronic coronary heart disease, and no evidence of congestive heart failure was seen, even in patients receiving large doses of propranolol. Nicardipine counteracted the potential deleterious effects of propranolol; increased peripheral vascular resistance and left ventricular stroke work and decreased cardiac output.     

Systemic and coronary hemodynamic effects of glucagon

The systemic and coronary hemodynamic effects of glucagon have been studied in anesthetized mongrel dogs. Administration of this agent produced an increase in cardiac rate, a decrease in systemic arterial pressure and increases in body and cardiac oxygen consumption. Arterial hemoglobin, hematocrit and oxygen content increased as did mixed venous oxygen content, but the coronary sinus oxygen content decreased. Cardiac output and coronary blood flow increased, but peripheral and coronary vascular resistances decreased. The systemic and coronary hemodynamic effects of glucagon were similar during beta adrenergic blockade induced by propranolol.     

Reproducibility of myocardial ischemia induced by atrial stimulation

Reproducibility of myocardial ischemia induced by atrial pacing (P) was investigated in 25 patients (pts) without previous anterior myocardial infarction and showing a positive exercise stress test. The second period of atrial pacing (P2) was exerted 20 minutes after the first (P1). During P2, a reduction in the parameters reflecting myocardial oxygen requirements (maximal left ventricular pressure, dp/dt max, TTI*HR values) was noted, while the signs of ischemia were less pronounced (ST depression decreasing from 2.3 +/- 1 mm to 1.6 +/- 1.0 mm; % of lactate extraction (%L) decreasing from - 6.4 +/- 25.5 to + 8.5 +/- 19.2; p less than 0.5). The 25 pts were divided into 2 groups according to the ejection fraction (EF greater than .55 16 pts Gr.F+; EF less than .55 9 pts Gr.F-). The distribution of coronary lesions was the same for the 2 groups. During P1 GR.F+ registered a negative % L as opposed to Gr.F-. During P2, the difference in the % L between the 2 groups was also significant (2.6 +/- 19.9% F+ vs 18.9 +/- 14.3% F-; p less than .05). Collateral circulation had no effect upon the results, neither for P1 or P2. This study shows that a second period of atrial pacing, 20 minutes after the first, induced lesser ischemia than the first period of atrial pacing. This phenomenon could explain the paradoxical improvement observed in certain patients after a first episode of angina. These results have implications as regards the necessity of double blind studies compared to placebo when using this technique in the evaluation of the effects of anti-ischemic drugs.     

Acute hemodynamic study of intravenous nicardipine in arterial hypertension

The acute hemodynamic effects of intravenous Nicardipine (N), a new calcium antagonist, were studied in 8 patients with moderate essential hypertension. The forearm arterial blood flow (ABF) was measured using plethysmography before and after N infusion: 1st step was obtained after infusion of 1 mg during 5 min then 1 mg during 25 min; a second step was obtained after the infusion of the same dose during the same time; thus a cumulative dosage of 4 mg was infused over a total duration of 60 mn. Systolic (SBP), diastolic (DBP) mean (MBP) blood pressure and heart rate (HR) were measured every minute using a non invasive device (Dinamap). Systemic vascular resistances (SVR) were calculated. Plasma concentration of N was determined at the beginning, in the middle and at the end of each step. Results are as follows: (table; see text) A 33% decrease in SVR was observed at the 2nd step whereas MBP decreased by 15% only. The date confirm the potent vasodilatory effect of intravenous N at low dosage; the BP alteration was moderate in relation to an increase in local blood flow. These results indicate that Nicardipine could be useful as part of the treatment of chronic arteriopathy and Raynaud disease.     

Abnormal coronary flow profiles at rest and during rapid atrial pacing in patients with hypertrophic cardiomyopathy

To examine the mechanism of myocardial ischemia in hypertrophic cardiomyopathy (HCM), coronary flow velocity was measured in the left anterior descending coronary artery (LAD) using a Doppler guide wire in 11 patients with HCM and in 8 normal controls. The average peak velocity (APV), percent increase of APV (%APV), and APV during systole (Vs) and diastole (Vd) were calculated at rest and during rapid atrial pacing. The APV in HCM reached a peak value at a heart rate of 90 beats/min, while in the controls the APV increased continuously until the heart rate reached 130 beats/min [%APV (130 beats/min); 103+/-30% in HCM vs 139+/-23% in controls, p<0.04]. During rapid atrial pacing, Vs in the controls increased, whereas Vs in HCM decreased further. During high-rate pacing, Vd in HCM reached a peak value at a heart rate of 90 beats/min, whereas in the controls, Vd increased continuously until the heart rate reached 130 beats/min. The acceleration rate of early diastolic flow was significantly lower in HCM than in the controls (1.85+/-0.66 vs 3.18+/-1.62 m/s2, p<0.03). This abnormal response might be due to an increase in the reverse systolic flow and a decrease in the diastolic flow, probably caused by a slow acceleration of early diastolic flow velocity in the LAD.     

Coronary and systemic hemodynamic effects of nicardipine

Systemic and coronary hemodynamic effects of a new dihydropyridine calcium antagonist, nicardipine, were studied in 15 patients. Nicardipine was administered as a 2-mg bolus intravenously followed by an infusion titrated to maintain a 10 to 20-mm Hg decrease in systolic pressure. Nicardipine increased both heart rate from 69 +/- 3 to 81 +/- 3 beats/min and cardiac output from 7.3 +/- 0.5 to 9.9 +/- 0.5 liters/min (both p less than 0.001) as systemic vascular resistance decreased from 1,183 +/- 70 to 733 +/- 33 dynes s cm-5 (p less than 0.001). Left ventricular end-diastolic pressure remained constant, at 14 +/- 1 vs 14 +/- 1 mm Hg as stroke volume increased from 108 +/- 6 to 123 +/- 6 ml/m2 (p less than 0.001). Coronary blood flow increased from 102 +/- 9 to 147 +/- 13 ml/min, while coronary resistance decreased from 1.17 +/- 0.1 to 0.7 +/- 0.1 mm Hg/ml/min (both p less than 0.001). Heart rate-systolic blood pressure product did not change (104 +/- 5 vs 106 +/- 5 beats/min mm Hg X 10(-2), difference not significant) with drug administration. At the same heart rate before and during nicardipine administration (using atrial pacing in 6 patients), significant augmentation of coronary flow was still observed. Thirteen of 14 patients showed a greater percent decrease in coronary resistance than systemic vascular resistance. Nicardipine differs from other calcium antagonists with respect to consistent augmentation of coronary blood flow. This effect appears to be the result, in part, of increased potency in the coronary bed compared with the systemic vascular bed.     

Hemodynamic study in hypertensive cardiopathy under ischemia induced by atrial stimulation in the absence of fixed coronary obstructions

With the purpose to study the haemodynamic changes that occur with myocardial ischaemia induced by atrial pacing (AP) in hypertensive heart disease, we studied 7 patients with such condition, all of them with a long time history of systemic hypertension, electrocardiographic signs at rest of left ventricular hypertrophy and ST-segment depression, at least of 0.5 mm. All the patients showed normal coronary arteries in angiocardiogram. AP was started 10 beats above the basal heart rate with increments of 10 beats every 2 minutes until a ST-segment depression at least of 2 mm was obtained which occurred in all the cases studied. After every 2 minutes of AP a simultaneous 12-leads electrocardiogram recording and left ventricular and aortic pull-back pressure were obtained. At the desired end point the AP was abruptly stopped and the same parameters were registered at 3, 5, 10 and 15 minutes until recovery. During AP the left ventricular systolic pressure (LVSP) did not show any significant change, with the exception of a patient who experienced angor pectoris during the proceeding. The left ventricular end-diastolic pressure (LVEDP) increased in 3.4 +/- 1.7 mmHg, change that was statistically significant (p less than or equal to 0.01) but not hemodynamically important since only in one patient it increased above the normal levels (from 13 mmHg basal to 17 mmHg during AP). In contrast, LVEDP markedly rose above normal when AP was stopped. It is concluded that neither LVEDP nor LVSP play an important role in the genesis of the ST segment depression seen in these patients. It is showed that, similar as in patients with obstructive coronariopathy, these cases work on a depressed Starling curve during AP and its recovery for what is thought that the functional meaning of ischaemia for both entities is similar no matter that their pathogenetic mechanisms are different.     

Systemic and coronary hemodynamic effects of beta-adrenoceptor blocking agents in coronary artery disease

Systemic and coronary hemodynamic effects of acebutolol (10 mg i.v.), a cardioselective beta-adrenoceptor blocking agent were investigated in 11 patients with coronary artery disease and significant arterial obstructive lesions. Efficacy was assessed by simultaneous left and right heart catheterization and with an inlaying Webster thermodilution catheter in the coronary sinus. The data were compared with data from 7 other patients who received 2 mg i.v. of propranolol, a non-cardioselective beta-blocker. With acebutolol, (1) the heart rate was reduced significantly (p less than 0.001), (2) no significant changes were observed in the LVSP, LVEDP, mean PWP, LVmax dp/dt/p, LV negative dp/dt/p, CI, SWI and SPI, (3) CSF and MVO2 decreased significantly (p less than 0.01) 5 min after injection and (4) the CVR showed a significant elevation (p less than 0.05) after 5 min. With propranolol, (1) the heart rate decreased significantly (p less than 0.05), (2) there were no significant changes in LVSP and LVEDP, (3) the mean PWP increased significantly (p less than 0.05), (4) the LVmax dp/dt/p, CI and SWI decreased significantly (p less than 0.05), (5) the CSF and MVO2 decreased markedly (p less than 0.01) and (6) the CVR increased markedly (p less than 0.01). As compared to the effects of 2 mg i.v. of propranolol, those produced by acebutolol (10 mg i.v.) were characterized by a predominant negative chronotropic action with minimal negative inotropic action, combined with a reduction in CSF and MVO2. The findings suggest that the efficacy of acebutolol in pump failure caused by myocardial ischemia during effort angina is mediated by improvement of the myocardial oxygen demand-supply imbalance.     

Haemodynamic effects of intravenous diltiazem at rest and exercise in patients with coronary artery disease

The acute effects of intravenous diltiazem on exercise performancewere studied in 10 patients with coronary artery disease. Haemodynamicmeasurements were made at rest and during exercise before andafter 0-5 mgkg^–1 of diltiazem. Diltiazem prolonged theduration of exercise (+2.85 min, P>0.001) and delayed theonset of ischaemic ST depression or angina in all patients.The highest tolerated heart rate and pressure rate product wereincreased in all but one patient after diltiazem. At rest diltiazem decreased mean arterial pressure (–10.8%,P>0.005), systemic vascular resistance (SVR) (-11.8%, P>005)and left ventricular stroke work index (SWI) (–14.1%,P>0.005). During exercise under diltiazem therapy, at the level achievedbefore the drug, the pulmonary capillary wedge pressure (-30%,P>0005) and the SVR (–13.6%, P>0.02) were lowered,the SWI (+13%, P>0.01) was increased: at the end of exerciseonly the SVR (14%, P>0.05) was reduced. Two patients experiencedangina on lying down and one had orthostatic hypotension afterexercise with diltiazem. This study indicates that intravenousdiltiazem is a potentially useful agent for the treatment ofangina by reducing myocardial oxygen demand at rest and by improvingleft ventricular performances on exercise.     

Comparative effects of intravenous dipyridamole and sublingual nitroglycerin on coronary hemodynamics and myocardial metabolism at rest and during atrial pacing in patients with coronary artery disease

The effects of intravenous dipyridamole (20 mg) and sublingual nitroglycerin (0.6 mg) were compared at rest and during rapid atrial pacing in patients with significant coronary obstruction. Dipyridamole, which had no significant effect on resting systolic blood pressure, caused a significant increase in coronary sinus flow (CSF) and reduction of coronary vascular resistance (CVR) and arterial-coronary sinus oxygen difference (AO₂-CSO₂δ), whereas nitroglycerin reduced resting systolic pressure but had no significant effect on CSF, CVR, or AO₂-CSO₂°. Although these effects of dipyridamole and nitroglycerin on resting systolic pressure, CSF, CVR, and AO₂-CSO₂° were qualitatively similar during rapid atrial pacing, the onset of chest pain and ischemic ECG changes occurred at a lower heart rate following dipyridamole (136±5 beats/min) than following nitroglycerin (149±6 beats/min, p<0.01). However, maximal double product and myocardial oxygen consumption achieved during pacing were similar following both dipyridamole and nitroglycerin and were less than control pacing values. Coronary dilatation following dipyridamole appears to reduce tolerance to pacing-induced ischemia probably by maldistribution of coronary flow away from ischemic myocardium. Nitroglycerin differs from dipyridamole by improving tolerance to pacing; however, this difference appears to be due to systemic vasodilator effects of nitroglycerin rather than to enhancement of flow to ischemic myocardium.     

Effects of diltiazem on cardiac and coronary circulation, at rest and during rapid auricular electric stimulation

The effects on cardiac performance and systemic and coronary blood flow of rapid atrial pacing alone and associated with an intravenous infusion of a slow calcium channel inhibitor, diltiazem, at a dose of 20 mg/kg were studied in 20 patients with chronic coronary artery disease. Atrial pacing increased coronary flow and myocardial oxygen consumption: it decreased coronary arterial resistance and the coronary arteriovenous difference in lactates. Left ventricular end diastolic pressure rose significantly compared to the basal state in the period following pacing. The administration of diltiazem was associated with a significant fall of femoral arterial pressure, of coronary arteriovenous difference and myocardial consumption of oxygen, and an increase in the coronary arteriovenous difference in lactate. Left ventricular end diastolic pressure did not differ significantly from the basal values recorded after terminating atrial pacing. Left ventricular end diastolic volume decreased. Diltiazem opposed or cancelled the undesirable effects of rapid atrial pacing with respect to coronary arteriovenous difference in lactate content. The beneficial action of diltiazem does not seem to be closely related to its hemodynamic effects. It could be related to a reduction in myocardial oxygen demands due to a decrease in systolic ventricular strain and the specific metabolic effects of the drug, and also to an increase in myocardial oxygen supply due to the reduction in left ventricular end diastolic stress and the coronary vasodilation caused by the drug.     

Systemic and splanchnic hemodynamic effects of intravenous hypertonic glucose in patients with cirrhosis

In animals, there may exist a hyperemic response in the portal circulation during intravenous administration of hypertonic glucose, but a hemodynamic response of this kind has never been described in man. This study was designed to evaluate if hyperglycemia itself could induce systemic or splanchnic hemodynamic changes in patients with cirrhosis. Sixteen patients with cirrhosis were studied before and during i.v. infusions of hypertonic (900 mOsmoles per liter) glucose (n = 8), mannitol (n = 4) or saline (n = 4) at 2 ml per min. In the group receiving glucose, there were significant increases in hepatic venous pressure gradient (+12%), azygos blood flow (+27%) and pulmonary capillary pressure (+32%), while calf blood flow decreased (-26%). No changes occurred in the mannitol or saline groups. Changes in plasma osmolality, plasma volume, splanchnic oxygen extraction and vasoactive hormones, including vasoactive intestinal polypeptide and glucagon, did not appear to be involved in the mechanism of these vasoactive phenomena. It is suggested that the possible deleterious effects of increase in portal pressure and azygos blood flow should be taken into consideration when administering hypertonic glucose to patients with portal hypertension.