Hemodynamic and myocardial effects of long-lasting venodilation in the conscious dog

Holtz, J.; Bassenge, E.; Kolin, Alexander

doi:10.1007/bf01906527

Cited by 37 publications

(11 citation statements)

References 23 publications

(20 reference statements)

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“…This decline causes lowered myocardial oxygen demands due to lowered myocardial wall tension and, additionally, improves the conditions for myocardial perfusion by lowering the extravaseular coronary resistance (22). This therapeutically favourable effect on cardiac preload results from the vasodilatory action of molsidomine, which does not involve dilating influences on total peripheral resistance or coronary resistance vessels (15,29). The dilation in the vessels of the low pressure system can be described quantitatively by the analysis of the effective compliance of the total vascular bed, thus allowing repeated studies in conscious animals on the effect of chronic venodilation.…”

Section: Discussionmentioning

confidence: 97%

“…Animal experiments (8,11,15,29) and clinical studies (5,19,20,(25)(26)(27) demonstrated that the reduction of intramyocardial wall tension due to lowered preload is the main therapeutic principle of the drug. Because of the documented long duration of its antianginal and venodilating action molsidomine may be a promising candidate for pharmacological prophylaxis of anginal attacks.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, experimental studies on venous vasomotor control in chronic preparations are desirable. The molsidomine-induced venodilation can be demonstrated in single veins in man (16) and animals (15). For the exact experimental analysis of the entire vascular low-pressure system, however, preparations under anesthesia with extensive surgical manipulations have been developed (11,30,31), which do not allow repeated analyses in the same subject during chronic studies.…”

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confidence: 99%

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Increased effective vascular compliance and venous pooling of intravascular volume during sustained venodilation in conscious dogs

et al. 1981

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The hemodynamic effects of the long-acting antianginal drug molsidomine were studied in 8 chronically instrumented conscious dogs by measuring the partition of the intravascular volume and the effective compliance of the total vascular bed. The blood volume of the resting dogs was varied by +/- 4 ml/kg in a cycle of blood infusion, withdrawal and reinfusion within 12 minutes. Relating the observed alterations in mean right atrial pressure to the induced changes in intravascular volume, an effective compliance of 2.9 +/- 0.4 ml. mm Hg-1 . kg -1 (mean +/- SD) was found. Heart rate, total peripheral vascular resistance and the local capacity of the distal femoral vein did not change significantly during the cycle of volume alterations. Following 0.1 mg/kg molsidomine i.v., mean right atrial pressure was lowered by 1.6 mm Hg and mean left atrial pressure by 3.4 mm Hg; the effective compliance was elevated to 4.7 +/- 0.6 ml . mm Hg-1. kg -1 (p less than 0.001), and the central blood volume was lowered from 17.8 +/- 3.1 to 14.8 +/0 3.3 ml/kg (p less than 0.01), while the total blood volume remained constant. The decline in stroke volume and the reflexly induced increase in heart rate correlated with the control heart rate. Mean arterial pressure declined from 101 +/- 7 to 91 +/- 14 mm Hg (p less than 0.05) and total peripheral vascular resistance remained unaffected. It is concluded that molsidomine exerts exerts its hypotensive effect by dilation within the vascular low-pressure system and that this dilation can be described quantitatively in conscious animals by the analysis of the total effective vascular compliance.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Increased effective vascular compliance and venous pooling of intravascular volume during sustained venodilation in conscious dogs

et al. 1981

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“…These doses are higher than those needed to evolve venous pooling and to reduce cardiac preload by reducing the cardiac filling pressure. In animal experiments, approximately 0.5 g/kg molsidomine is necessary to observe significant effects on peripheral resistance [21]. Only then can a decrease in the arterial pressure be demonstrated that exceeds the concomitant reduction in cardiac output.…”

Section: Sin-1 Dose-response Changes In Hemodynamic Resistive and mentioning

confidence: 97%

Effects of SIN-1 on peripheral hemodynamics and viscoelastic properties of aorta in anesthetized rabbits

Friggi

Bodard

Berenger

et al. 1989

Cardiovasc Drug Ther

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In closed-chest, non-barbiturate-anesthetized rabbits, we have used a computer-based parameter estimation method to evaluate the effects of a slow intravenous infusion of SIN-1 (15 micrograms/kg/min for 20 minutes) upon hemodynamic, geometric, viscoelastic, and energetic characteristics of the hindlimb arterial bed from the measurement of abdominal aortic diameter, blood flow, and blood pressure. To evaluate intrinsic effects of SIN-1 upon arterial wall characteristics, a moderate arterial bleeding (3 ml/kg) was performed to achieve a -10% lowering of arterial pressure, i.e., to reach an equivalent blood pressure reference threshold in the absence of the drug. The SIN-1 IV infusion induced a marked blood pressure lowering (-10.0 +/- 2.1%), resulting from a relaxing action on smooth muscle vasculature both in capacitive and resistive components of the hindlimb vascular tree, thereby eliciting a lowering in peripheral resistance (-22.8 +/- 3.1%) and an increased blood flow (+11.7 +/- 3.6%). SIN-1 enhanced vascular compliance (+28.0 +/- 2.2%) and lowered vascular input impedance (-31.2 +/- 8.9%), as confirmed by modulus and phase spectra. SIN-1 IV infusion contrasted bleeding effects by increasing blood flow and maintaining constant or increasing aortic diameter, both of them being lowered by bleeding. The relaxing effect elicited by SIN-1 was further demonstrated by changes in viscoelastic characteristics, and it was further associated with a decreasing energetic demand as well. The present results demonstrated that SIN-1, administered as a slow IV infusion, exhibits vasodilating properties by acting both on capacitive and resistive vessels of the systemic circulation.

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“…It seemed therefore of importance to clarify whether molsidomine, another long-acting vasodilator with a peripheral site of action similar to ISDN (14), would elicit counterregulatory mechanisms. Molsidomine exerts its antianginal effect via lowering of the venous return by dilation of the capacitance vessels, leading to diminished ventricular volume, a decrease in cardiac output and, hence, a decrease in myocardial oxygen consumption (2,8,14,9). *) A preliminary report of this study has been presented at the 21st Spring Meeting of the Deutsche Pharmakologisehe Gesellschaft (Naunyn-Schmiedeberg's Arch.…”

Section: Introductionmentioning

confidence: 99%

The effect of repeated intravenous and oral doses of molsidomine (N-carboxy-3-morpholino-sydnonimine-ethylester) on plasma renin activity and plasma catecholamine levels in conscious dogs

et al. 1983

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The responses of plasma renin activity (PRA) and plasma catecholamine levels to molsidomine, administered both intravenously and orally, were investigated in conscious trained dogs. Intravenous administration of molsidomine at increasing dosage up to 0.4 mg/kg with a constant dose interval of 4 hours did not lead to a sustained increase in PRA. By contrast, a significant increase in PRA was still present after 4 hours on administration of 0.4 mg/kg molsidomine by the oral route. This longer-lasting increase in PRA following oral administration is discussed in relation to the conversion of molsidomine to an active metabolite in the liver. A reduction of dose interval to 3 hours or less led to a marked cumulative increase in PRA. It appears that substances acting via venous pooling lead to persistent activation of the renin angiotensin aldosterone system (RAA system), which counteracts its primary therapeutic effect. A slight increase in plasma noradrenaline levels was observed in response to repeated oral administration of 0.4 mg/kg molsidomine at a dose interval of 2 hours, indicating participation of the sympathetic nervous system in the counterregulatory process.

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Hemodynamic and myocardial effects of long-lasting venodilation in the conscious dog

Cited by 37 publications

References 23 publications

Increased effective vascular compliance and venous pooling of intravascular volume during sustained venodilation in conscious dogs

Increased effective vascular compliance and venous pooling of intravascular volume during sustained venodilation in conscious dogs

Effects of SIN-1 on peripheral hemodynamics and viscoelastic properties of aorta in anesthetized rabbits

The effect of repeated intravenous and oral doses of molsidomine (N-carboxy-3-morpholino-sydnonimine-ethylester) on plasma renin activity and plasma catecholamine levels in conscious dogs

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