Intravenous administration of large dosages of adenosine or adenosine triphosphate with minimal blood pressure fluctuation.

Hemodynamic responses, blood gas, and metabolic changes were assessed when large dosages of a pre-mixed solution of adenosine or adenosine triphosphate (ATP) with catecholamine were intravenously administered in the conscious, spontaneously breathing rabbit. The present study offers a simple and effective approach to enabling safe administration of large doses of the potent vasodilators, adenosine or ATP with minimal cardio-respiratory and metabolic changes.

Negative inotropic effects of ATP on the isometric contractions of isolated rat heart muscle.

The effects of ATP on the isometric contractions of isolated rat left ventricular papillary muscle were studied. Exogenously administered ATP had an immediate onset, an abrupt response, progressive recovery and produced dose-related depression in the peak developed tension, maximum rate of tension development and relaxation, which were statistically significant. There were no significant changes in the resting tension, time to peak tension and relaxation time, except for a significantly prolonged relaxation time at the highest concentration of ATP. In the studies of interactions of ATP and either epinephrine or Ca(++), we observed that ATP seemed to interfere with the inotropic effect of epinephrine, while Ca(++) antagonized the negative inotropic action of ATP. We conclude that the site of negative inotropic action of ATP is most likely on the cell membrane, where ATP interferes with Ca(++) flux, and that ATP interferes with the positive inotropic action of epinephrine.

Prevention of hypertensive crisis with ATP during anesthesia for pheochromcytoma.

In the anesthetic management of five patients undergoing excision of pheochromocytoma, adenosine triphosphate (ATP) was used for the purpose of regulating systemic arterial pressure during the period of tumor manipulation. ATP was administered at doses of 0.05-0.4 mg/kg/min. Systemic arterial pressure showed a significant decrease from 162 +/- 17/103 +/- 11 mmHg before manipulation to 136 +/- 21/81 +/- 10 mmHg during the manipulation period. The plasma catecholamine levels showed significant increases in this period. Immediately after excision, the systemic arterial pressure was maintained at normal levels (118 +/- 13/75 +/- 16 mmHg) by fluid replacement and discontinuation of ATP administration, subsequently becoming 129 +/- 19/79 +/- 16 mmHg. The heart rate was very stable and tachycardia did not occur during the manipulation period. Only one arrhythmic episode occurred in one patient. The systemic vascular resistance index was significantly lower during the manipulation period than before it. It was therefore considered that ATP was useful as an agent for controlling arterial pressure during the anesthesia for pheochromocytoma.

Myocardial hemodynamics during induced hypotension: a comparison between sodium nitroprusside and adenosine triphosphate.

Adenosine triphosphate (ATP) has been reported to be a hypotensive agent similar in effect to sodium nitroprusside (SNP). The purpose of this study was to examine and compare the effects of both SNP and ATP on general coronary hemodynamics, myocardial O2 consumption, and circulating catecholamines. Twelve dogs were anesthetized with 1.0% halothane and given either SNP or ATP by controlled infusion to reduce their systemic blood pressure by 50% for a 2-h period followed by a (blood pressure) recovery period. The ATP-induced hypotension was rapid, easily controlled, not accompanied by tachyphylaxis over the 120 min studied, and resulted in an increase in coronary sinus blood flow (CSBF), which plateaued at 260% above control. The increase in CSBF was almost immediate and remained at this elevated level for the duration of the induced hypotension. During the ATP-induced hypotension, there was no change in heart rate or circulating catecholamines. A 60% reduction in myocardial O2 uptake was observed, presumably from the cardiac unloading. In contrast, SNP-induced hypotension required a marked increase in dose over time, did not significantly increase CSBF, did increase heart rate, and resulted in large increases in circulating plasma catecholamines. Neither agent affected cardiac output. ATP-induced hypotension resulted in no change in cardiac lactic acid uptake, while SNP caused lactic acid production, indicating possible cardiac ischemia or cyanide toxicity.

Hypotensive effects of adenosine and adenosine triphosphate compared with sodium nitroprusside.

Hypotensive effects of the intravenous injection of adenine compounds [adenosine triphosphate (ATP), adenosine] were compared with those of sodium nitroprusside (SNP) in rabbits during light, stable halothane anesthesia. ATP and adenosine were almost equipotent in their effects on blood pressure and heart rate. The hypotensive potencies of ATP and adenosine were approximately 1/6 (bolus injection) and 1/40 (continuous infusion) that of SNP, but the adenine compounds had a more rapid onset of action and shorter recovery times than SNP. With bolus injection, SNP invariably caused a baroreceptor-mediated reflex increase in heart rate. In contrast, ATP and adenosine caused a dose-related decrease in heart rate and hypotension. With continuous infusion, ATP and adenosine produced immediate onset of hypotension without tachycardia. Blood pressure remained remarkably stable throughout the infusion; neither tachyphylaxis nor rebound hypertension were observed. Thus, the adenine compounds offer possible advantages over SNP as they are physiologic agents with little or no acute toxicity and may be devoid of tachycardia, tachyphylaxis, and rebound hypertension.