Hemodynamic effects of amrinone in children after cardiac surgery

The hemodynamic effects of amrinone were assessed in seven children following cardiac surgery. Amrinone was administered as a bolus of 1 mg kg^–1 body wt., followed by continuous infusion at 10 g kg^–1 min^–1 for 1 h and two stepwise increases to 20 and 40 g kg^–1 min^–1 for 30 min each. Hemodynamic data were obtained and plasma concentrations of amrinone measured 1 h after the bolus dose and immediately before each increment of the infusion rate. Amrinone levels ranged from 0.7 to 2.3 mgl^–1. Administration of amrinone lowered systemic vascular resistance from 20.0±4.3 to 16.5±4.6 mmHgl^–1 min^–1m^–2 (p<0.05) and reduced mean arterial pressure from 71.7±9.5 to 62.6±13.5 mmHg (p<0.05) at the highest infusion rate, confirming the known vasodilative effect of the drug. However, these effects did not result in a statistically significant increase in stroke volume (35.0±7.5 to 35.5±7.0 ml m^–2, NS) or cardiac index (3.10±0.50 to 3.20±0.40 l min^–1 m^–2). One additional patient, in whom a higher loading dose was tried in order to achieve a higher plasma concentration, developed systemic hypotension. A correlation was established between the plasma concentrations of amrinone and the percentage decrease in systemic resistance (r=0.70,p<0.05). These results suggest that in children after open heart surgery, amrinone acts primarily as a systemic vasodilator, with questionable inotropic effect. Accordingly, its use should be restricted to children with severe cardiac failure and documented highly elevated afterload.     

Hemodynamic effects of antidysrhythmic drugs

Antidysrhythmic medications, when administered in the clinical setting, demonstrate a variety of effects on cardiac electrophysiology, inotropy, and peripheral vascular smooth muscle. The resultant hemodynamic effects may be of profound importance to the clinical well-being of the patient being treated for dysrhythmias. The following review will discuss the hemodynamic effects of the Class I agent moricizine; Class IA agents: quinidine, procainamide hydrochloride, and tocainide hydrochloride; Class IC agents: flecainide acetate, encainide hydrochloride, and propafenone; Class II agents: propranolol hydrochloride, esmolol hydrochloride, and acebutolol; Class III agents: bretylium tosylate and amiodarone hydrochloride; as well as the Class IV agent verapamil. Adenosine, an unclassified antidysrhythmic indicated in the treatment of supraventricular tachycardia will also be discussed. Specific attention will be directed toward the use of these agents in patients with left ventricular dysfunction or history of congestive heart failure.     

Hemodynamic effects of ventricular defibrillation

Hemodynamic responses to ventricular defibrillation were studied in anesthetized dogs. Observations were made on arterial, right atrial and left ventricular end-diastolic pressures, on cardiac output (dye dilution), heart rate, and right atrial electrocardiogram. Ventricular fibrillation was induced electrically with a bipolar electrode catheter placed in the right ventricle. Fibrillation was maintained for 15 or 30 sec and terminated with a 400 w sec capacitor discharge across the thoracic cage.Responses lasted 1-10 min after conversion and included a cholinergic and an adrenergic component. The cholinergic component was characterized by sinus bradycardia, periods of sinus arrest, atrioventricular block, and ventricular premature beats. The adrenergic component included increases in arterial pressure, in cardiac output, and in left ventricular stroke work at a time when left ventricular end-diastolic pressure was normal; there was no change in total peripheral resistance. The pH of arterial blood decreased slightly and pCO(2) increased but pO(2) and the concentration of lactate were unchanged. Bilateral vagotomy and intravenous administration of atropine blocked the cholinergic component, unmasked a sinus tachycardia, and accentuated the adrenergic component of the response. The latter was blocked by intravenous administration of propranolol and phenoxybenzamine.THESE RESPONSES WERE RELATED PRIMARILY TO CONVERSION OF VENTRICULAR FIBRILLATION RATHER THAN TO THE ELECTRICAL DISCHARGE OF COUNTERSHOCK BECAUSE COUNTERSHOCK WITHOUT VENTRICULAR FIBRILLATION CAUSED MORE TRANSIENT AND SMALLER RESPONSES THAN THOSE OBSERVED WITH DEFIBRILLATION: furthermore, the hemodynamic effects of defibrillation were augmented by prolongation of the duration of fibrillation. The results suggest that the cholinergic component of the response may be detrimental in that it favors spontaneous recurrence of fibrillation; on the other hand, the adrenergic component may be essential for conversion since only one of six dogs depleted of endogenous catecholamines with reserpine survived ventricular defibrillation.     

Hemodynamic effects of antihypertensive drugs

Elevated total peripheral resistance and normal cardiac output are the hemodynamic characteristics of chronic essential hypertension. One approach to treating hypertension matches the individual pathophysiology with the hemodynamic effects of antihypertensive drugs. Antiadrenergic drugs are appropriate second-step therapy in many cases of established hypertension; by reducing total peripheral resistance, these agents can reduce blood pressure while sparing cardiac output and renal blood flow. The physician should treat elderly hypertensive patients cautiously and consider using drug with a favorable hemodynamic profile.     

Hemodynamic and humoral effects of coffee after beta 1-selective and nonselective beta-blockade

Several studies report a substantial rise in plasma catecholamines after caffeine. Epinephrine infusion induces a pressor response after nonselective beta-blockade. We studied the hemodynamic and humoral effects of drinking coffee after placebo and after both nonselective (propranolol) and beta 1-selective (metoprolol) blockade in 12 normotensive subjects. After placebo, coffee induced a rise in systolic and diastolic blood pressure and a fall in heart rate, whereas forearm blood flow did not change. Plasma catecholamines, especially epinephrine (+150%), rose and plasma renin activity, fell after drinking coffee. The effects of coffee on blood pressure, forearm blood flow, and all humoral parameters were not altered by pretreatment with propranolol or metoprolol. The fall in heart rate after coffee, however, seemed to be greater during propranolol. We conclude that the rise in plasma epinephrine after coffee was too small to reveal differences in reaction in propranolol- and metoprolol-pretreated subjects.     

Hemodynamic and metabolic effects of dobutamine in 18 patients after open heart surgery

Low cardiac output syndrome frequently follows cardiopulmonary bypass (CPB) surgery. In the present study, we used dobutamine to increase cardiac index (CI) and oxygen delivery (DO2) in 18 patients after open heart surgery. Using increasing doses of dobutamine up to 10 micrograms/kg.min-1, we observed statistically significant (p less than .01) increases in mean CI (2.50 +/- 0.10 to 3.56 +/- 0.18 L/min.m2) and in mean heart rate (HR) (83 +/- 3 to 105 +/- 3 beat/min). Mean systemic vascular resistance index decreased significantly (p less than .01) in all patients (2271 +/- 101 to 1648 +/- 83 dyne.sec/cm5.m2). Pulmonary vascular resistance index did not change in the ten coronary artery bypass graft patients, but decreased significantly (p less than .01) in the eight valve replacement patients (561 +/- 98 to 421 +/- 79 dyne.sec/cm5.m2). Mean DO2 increased in all patients, although there was no concomitant increase in oxygen consumption (VO2) in four patients. We observed a significant (p less than .01) increase in mean VO2 in the remaining 14 patients (110 +/- 6 to 148 +/- 12 ml/min.m2), in spite of significant decreases in PaO2 and increases in right-to-left intrapulmonary shunting. Although increases in HR and ventricular arrhythmias may limit its use, dobutamine increases CI and DO2 in patients after CPB. In the present study, dobutamine's varying metabolic effect exemplifies the need for close monitoring of hemodynamic and metabolic variables when using vasoactive drugs in the postoperative period.     

Hemodynamic effects of microbubble echo contrast

The dose-related hemodynamic effects of an active (bubble-rich) echo contrast agent were compared with those of a bubble-free contrast agent and saline solution to determine whether the microbubbles contained in the echo contrast agent are truly passive indicators in the circulation or whether they actively alter the hemodynamic state independent of the volume and osmotic loading associated with such injections. The study population consisted of 13 fully instrumented open-chest mongrel dogs. Four hundred ninety-two bolus injections were made of three different types: active contrast agent (Levovist, Schering AG, Berlin) (n = 333), saline solution (n = 112), and bubble-free contrast agent (n = 47). Levovist was administered in five dose ranges spanning 0.013 to 0.341 gm/kg and, like the saline solution, was administered in bolus volumes of 0.053 to 1.136 ml/kg. For each injection type, the percent change in hemodynamic parameters after administration of the bolus were calculated on the basis of the dose or volume of the injectate. Audio Doppler signal intensity was used to document the presence of bubbles in the injectate. Statistical significance was defined at the p = 0.05 level; clinical significance was defined as a greater than 15% change in a hemodynamic parameter. Statistically, but not clinically, significant changes were noted in almost all hemodynamic parameters regardless of injection type, and at all dose and volume ranges. Although statistically significant, injection of an active contrast agent in the human dose range resulted in a <5% change in hemodynamic parameters. High doses of a contrast agent (active or bubble-free) increased the left atrial pressure and had associated changes in peripheral vascular hemodynamics because of the osmotic load. Clinically significant increases (>15%) in pulmonary artery pressure and pulmonary vascular resistance were unique to the active contrast agent at high dose ranges. Standard doses of the active contrast agent changed the hemodynamics by less than 5% in healthy dogs. Transient clinically significant increases in pulmonary artery pressure and pulmonary vascular resistance are a unique side effect to high dose bolus injections of microbubble echo contrast agent.     

丹参酮抑制钙调蛋白信号传导系统在心肌梗死后恶性心律失常中的作用

目的：观察丹参酮对心肌梗死家兔模型恶性心律失常的作用,并探讨丹参酮导致的钙调蛋白（CaM）信号传导系统改变与恶性心律失常发生率降低之间的关系。方法选取健康大耳家兔共90只,随机分为3组：心肌梗死模型家兔（无干预组）、心肌梗死丹参酮干预家兔（干预组）和假手术对照家兔（对照组）,每组30只。对3组家兔恶性心律失常发生率、CaM、钙调蛋白激酶Ⅱ（CaMK-Ⅱ）活性、跨室壁复极离散度（TDR）、心肌细胞内 Ca2＋浓度进行统计并比较。结果对照组未发生恶性心肌梗死,无干预组和干预组恶性心律失常发生率均高于对照组,差异有统计学意义（P ＜0．05）;无干预组恶性心律失常率（60．0％）高于干预组（10．0％）,差异有统计学意义（P ＜0．05）。无干预组和干预组家兔的 CaM 蛋白水平分别是对照组家兔的1．483倍和1．321倍,差异均有统计学意义（P ＜0．05）;无干预组家兔 CaM 蛋白水平高于干预组,差异有统计学意义（P ＜0．05）。3组间 CaMKⅡ的活性比较差异无统计学意义（P ＞0．05）。无干预组血清钙离子水平高于对照组和干预组,差异有统计学意义（P ＜0．05）;干预组低于无干预组,差异有统计学意义（P ＜0．05）。干预组 TDR 低 于 无 干预组,这两组 TDR 均高于对照组,差 异 有 统 计 学意义（P ＜0．05）。干预组梗死心肌单细胞水平胞内钙浓度低于无干预组,差异有统计学意义（P ＜0．05）。结论CaM 信号传导系统的相关信号因子的水平对心肌梗死后恶性心律失常有提示作用。丹参酮可以通过抑制 CaM 信号传导系统而在预防心肌梗死后恶性心律失常中发挥重要作用。     

Hemodynamic effects of naloxone in anaphylactic shock

Recent reports suggest that endorphins may contribute to hemodynamic depression in septic and hemorrhagic shock. There is also evidence that reversal of endorphin effects with high dose naloxone may improve hemodynamic function and improve survival in shock states. The purpose of this study was to examine the effects of naloxone on hemodynamic parameters in anaphylactic shock. Anaphylactic shock was induced in sensitized rabbits with horse serum. Three minutes after serum challenge, rabbits were treated with a 3 mg/kg bolus of naloxone followed by a 3 mg/kg per h infusion (group I, n = 8), or by injection with an equal volume of saline (group II, n = 8). Cardiac output, blood pressure, heart rate and body temperature were monitored continuously for 60 min and the experiment was terminated. There was a significant increase in cardiac index in group I animals at 10 min (P less than 0.01) and 15 min (P less than 0.01). Stroke volume index was also higher in naloxone treated animals at 10 min and 15 min (P less than 0.05). Although mean blood pressure was higher in group I animals at all time intervals after naloxone was begun, the difference was statistically significant only at 60 min (P less than 0.05). Peripheral vascular resistance index was not significantly different for the two groups.     

Hemodynamic effects of phenoxybenzamine in anesthetized dogs

Our studies demonstrated that phenoxybenzamine, 10 mg/kg, administered intravenously to intact anesthetized dogs, produced an immediate and significant increase of heart rate and cardiac output. In heart-lung preparations, phenoxybenzamine had no effect or a negative cardiac inotropic effect, hence these actions were not related to direct cardiac action or to release of myocardial norepinephrine stores. Serial estimations of arterial blood catecholamines after phenoxybenzamine showed an increase of epinephrine and norepinephrine; the peak values of these catecholamines did not correlate well with the maximum cardiac output responses. Ganglionic blockade largely eliminated the early cardiac effects of phenoxybenzamine, hence its action did not appear to be upon peripheral terminals of postganglionic sympathetic or parasympathetic nerves. Phenoxybenzamine was found to have antivagal actions which might account for some of the delayed cardiac acceleration. When beta adrenergic receptor blockade was induced by sotalol, the cardiac effects of phenoxybenzamine were largely eliminated. Baroreceptor denervation prevented the increase of cardiac output after phenoxybenzamine. These observations are consistent with the concept that the increase of cardiac rate and output produced by phenoxybenzamine is principally mediated by baroreceptor reflexes acting through sympathetic cardiac nerves or circulating catecholamines.     

Hemodynamic effects of pyruvate infusion in dogs

Although pyruvate supplementation enhances endurance in humans and increases cardiac output in dogs, its effects on cardiac and peripheral vascular function are not known. Thus, we assessed the cardiovascular effects of pyruvate infusion.

Aortic, left ventricular (LV), and pulmonary (Ppa) pressures and LV stroke volume (Sv_lv; derived from aortic flow probe) were measured after thoracotomy in eight anesthetized dogs. LV area or volume changes were measured using either an epicardial echocardiography (n = 6) or a conductance catheter (n = 2). LV end-systolic elastance (Ees_lv) and preload recruitable stroke force (PRSF_lv) relations, as estimates of contractility, were generated by transient inferior vena cave occlusion. Simultaneous stroke volume to arterial pressure relations during the occlusions were used to measure arterial elastance (Ea), and steady-state systemic and pulmonary vascular resistances were used as measures of arterial tone. Graded doses of pyruvate (8, 16, and 32 mg/kg/min), dobutamine (positive control) and propranolol (negative control) and placebo (volume control) were sequentially given.

Dobutamine increased Ees_lv PRSF_lv, whereas propranolol had the opposite effect on Ees_lv and PRSF_lv. Pyruvate at 32 mg/kg/min increased heart rate, Ppa, and SV_lv and decreased LV end-diastolic area, and systemic vascular resistance without changing arterial pressure, Ees_lv PRSF_lv. or Ea.

We conclude that pyruvate infusion in normal dogs induces venodilation but does not alter either cardiac contractility or arterial tone.