Hemodynamic effects of isoproterenol in canine endotoxin shock

Abstract

A B S T R A C T Myocardial function and peripheral hemodynamic alterations were measured through the late stages of canine endotoxin shock. 60 min postendotoxin paired animals were given infusions of either 5 ml/kg per hr of 5%o dextrose or dextrose plus isoproterenol (0.25 pg/kg per min). Comparable blood lactic and pyruvic acid levels were determined, the excess lactic acid calculated, and pH values were obtained. During the initial stages the classic pattern of hemodynamic alterations was observed; an excess of lactic acid appeared and the pH decreased. Outstanding was evidence of markedly reduced myocardial function in the late stages of shock with progressive rise in left ventricular end diastolic pressure (LVEDP), low cardiac index, rise of central venous pressure, increased central blood 'volume, tachycardia, and declining arterial pressure. Analyses of left ventricular function curves also indicated myocardial failure.Infusion of dextrose alone failed to decrease mortality rate (10 of 18 dying), whereas the rate was significantly decreased with isoproterenol (2 of 18). Dextrose infusion did not benefit myocardial function. Isoproterenol resulted in a marked improvement in myocardial action with a significant increase in heart work associated with, yet very minor, increments of LVEDP. In addition, tachycardia subsided, peripheral resistance decreased, and the blood pressure stabilized. The Address requests for reprints to Dr.

A Reappraisal of Isoproterenol in Goal-Directed Therapy of Septic Shock

“…Stroke index paralleled the changes in cardiac index. In 23 patients with bacteriemic shock treated with isoproterenol (1.5 to 18.0 2gIminute j1 ), cardiac index and stroke index increased by 47% and 22%, respectively, with no significant decrease in mean arterial pressure (14). Similar modifications were observed in the present study.…”

“…For that purpose, potent drug acting on beta-1 cardiac receptor should be used. The reliable and marked effect of isoproterenol on beta receptors has been highlighted in experimental models (14), and in patients with shock (15). Endotoxemic dogs treated with isoproterenol showed a progressive rise in cardiac index, reaching a maximum after 7 hours, of 42% above the baseline.…”

Simple and Combined Adrenergic Receptor Blockade in Canine Endotoxinemia

“…In the present experiments the administra tion of a lethal dose of endotoxin produced only trivial falls in total sys temic and femoral arterial conductances (table II) which were invariably accompanied by a rise in hematocrit. In the absence of a gross vascular response, hypotension was likely to be related to reduction in cardiac output secondary to myocardial weakening [23,25] or to diminished ve nous return caused by hepatic venoconstriction [3] or by plasma loss [4]. There appears to be little support for the hypothesis [26] that vaso dilator agents are necessary in the treatment of acute canine endotoxine mia and our observations are consistent with the assumption that the beneficial effect of isoproterenol is related to actions other than systemic vasodilatation [25], Similar to the experiments reported by Spink et al [24], the level of circulating catecholamines was not excessively high in our animals and was considerably lower than in bled dogs [10].…”

“…In the absence of a gross vascular response, hypotension was likely to be related to reduction in cardiac output secondary to myocardial weakening [23,25] or to diminished ve nous return caused by hepatic venoconstriction [3] or by plasma loss [4]. There appears to be little support for the hypothesis [26] that vaso dilator agents are necessary in the treatment of acute canine endotoxine mia and our observations are consistent with the assumption that the beneficial effect of isoproterenol is related to actions other than systemic vasodilatation [25], Similar to the experiments reported by Spink et al [24], the level of circulating catecholamines was not excessively high in our animals and was considerably lower than in bled dogs [10]. This, and the observation that reserpine premedication fails to improve toler ance to endotoxinemia [15] support the assumption that the toxic effect of endotoxin is not caused primarily by the action of increased catecho lamine release [24],…”

Studies in clinical shock and hypotension

“…Not only will myocardial infarction and pulmonary embolism directly alter cardiac performance, but hemorrhagic, traumatic, and septic shock also may be accompanied by hemodynamic evidence of myocardial deterioration (1)(2)(3)(4)(5). Cardiac failure in shock has been variously attributed to a reduction of coronary blood resulting from lowered aortic pressure (6)(7)(8)(9), to the myocardial depressant effect of humoral substances (9,10), and to derangements in acid-base balance (11,12).…”