Cardiac and vascular effects of diltiazem, dobutamine and amrinone, drugs used after myocardial revascularization.

Hemodynamic care during postoperative management of myocardial revascularization should include vasorelaxing drugs to insure adequate graft and coronary flow, and stimulation of stroke volume to maintain vascular perfusion pressure. We tested the cardiac (inotropic and lusitropic) and vascular (relaxant) effects of diltiazem (0.1 nM to 0.1 mM), dobutamine (10 microM to 10 mM) and amrinone (10 microM to 1 mM) on isolated rat atria and thoracic aorta, and also on isolated human saphenous vein (HSV) and human mammary artery (HMA). Dobutamine produced a maximal positive inotropic effect (+dF/dt max = 29 +/- 7%) at its ED50 for aortic relaxation (88 +/- 7 microM). Conversely, at their ED50 for aortic relaxation diltiazem depressed myocardial contractility and amrinone did not exhibit myocardial effects. In HSV and HMA contracted with 80 mM potassium, diltiazem and dobutamine (but not amrinone) had a vasorelaxant activity similar to that in rat aorta. Norepinephrine-contracted human vessels were significantly more sensitive than potassium-contracted vessels to the relaxant effect of amrinone (ED50 HMA = 15 +/- 5 microM, ED50 HSV = 72 +/- 31 microM, P < 0.05). We conclude that at concentrations still devoid of myocardial effects dobutamine and amrinone are effective dilators in graft segment vessels and rat aorta contracted by membrane depolarization. If the difference between aortic and myocardial tissue still holds in human tissues, at the appropriate concentrations these drugs should be expected to improve cardiac performance while still contributing to the maintenance of graft patency.

Cardiac and vascular effects of diltiazem, dobutamine and amrinone, drugs used after myocardial revascularization

Hemodynamic care during postoperative management of myocardial revascularization should include vasorelaxing drugs to insure adequate graft and coronary flow, and stimulation of stroke volume to maintain vascular perfusion pressure. We tested the cardiac (inotropic and lusitropic) and vascular (relaxant) effects of diltiazem (0.1 nM to 0.1 mM), dobutamine (10 æM to 10 mM) and amrinone (10 æM to 1 mM) on isolated rat atria and thoracic aorta, and also on isolated human saphenous vein (HSV) and human mammary artery (HMA). Dobutamine produced a maximal positive inotropic effect (+dF/dt max = 29 ñ 7 percent) at its ED50 for aortic relaxation (88 ñ 7 æM). Conversely, at their ED50 for aortic relaxation diltiazem depressed myocardial contractility and amrinone did not exhibit myocardial effects. In HSV and HMA contracted with 80 mM potassium, diltiazem and dobutamine (but not amrinone) had a vasorelaxant activity similar to that in rat aorta. Norepinephrine-contracted human vessels were significantly more sensitive than potassium-contracted vessels to the relaxant effect of amrinone (ED50 HMA = 15 ñ 5 æM, ED50 HSV = 72 ñ 31 æM, P < 0.05). We conclude that at concentrations still devoid of myocardial effects dobutamine and amrinone are effective dilators in graft segment vessels and rat aorta contracted by membrane depolarization. If the difference between aortic and myocardial tissue still holds in human tissues, at the appropriate concentrations these drugs should be expected to improve cardiac performance while still contributing to the maintenance of graft patency.

[Structural and functional aspects of the human saphenous vein used as aorto-coronary graft in myocardial revascularization]. / Aspectos estructurales y funcionales de la vena safena humana utilizada como puente aorto-coronario en la cirugia de revascularización miocárdica.

The human saphenous vein (HSV) is currently used as a graft in coronary revascularization as well as in some other vascular beds, namely those of the inferior limbs. Since a significant proportion of HSV grafts develop stenosis, many studies have focused on the factors that could promote graft failure. This article reviews the results on structural and functional features that might be concurrent in the production of saphenous vein graft stenosis. The reactivity of HSV to several physiological agonists is analyzed, including those derived from the endothelium with contractile or relaxing properties, since these are relevant inducers of graft spasm and/or modifiers of the expression of graft factors involved in either tissue growth or thrombotic-atherosclerotic processes. Mechanisms that regulate vascular smooth muscle contractile state, in particular the activity of K+ channels of the plasma membrane, are described.

The antineoplastic agent paclitaxel (Taxol) increases contractile activity in human saphenous veins and human mammary arteries.

Effects of the antineoplastic agent paclitaxel (Taxol) were studied on contractions of isolated human saphenous vein (HSV) and mammary artery (HMA). Peak force developed by vascular segments with cumulative concentrations of physiologic agonists was enhanced by paclitaxel, producing a shift to the left of dose-response curves. Paclitaxel 1 microM decreased ED50 (in microM) for norepinephrine from 1.01 +/- 0.24 to 0.20 +/- 0.06 (n = 16, p < 0.05) in HSV and from 1.30 +/- 0.30 to 0.51 +/- 0.21 (n = 15, p < 0.05) in HMA and for 5-hydroxytriptamine from 0.64 +/- 0.19 to 0.21 +/- 0.07 (n = 20, p < 0.05) in HSV. Paclitaxel 1 microM also significantly increased the peak force of contractions elicited by endothelin-1 0.01 microM in HSV. In contrast, it did not affect contractions evoked by KCl 80 mM. These results show that paclitaxel produces a hyperreactivity in human vessels challenged by physiologic agonists, which suggests that administration of paclitaxel to patients could augment peripheral resistance and increase blood pressure.

Mechanical properties of human saphenous veins from normotensive and hypertensive patients.

BACKGROUND: Different reactivities of saphenous vein grafts in hypertensive and normotensive patients could lead to differences in the postoperative patency of the grafts. METHODS: In saphenous vein rings isolated from remnants of aorta-coronary grafts obtained from hypertensive and normotensive patients we studied the length-tension relationship; response to high levels of potassium, norepinephrine, and epinephrine; and relaxation in response to calcium deprivation. RESULTS: The rings from hypertensive patients were stiffer and developed more force (grams force/grams weight) than the rings from normotensive subjects to 80 mmol/L potassium (59+/-16 versus 25+/-5, p < 0.05) and to 1 micromol/L norepinephrine (61+/-8 versus 36+/-7, p < 0.05), but not to 10 micromol/L epinephrine (57+/-11 and 54+/-11; not significant). The rings from hypertensive patients relaxed more slowly than those of the normotensive subjects in a calcium-free medium (time to half-relaxation of 976+/-180 versus 548+/-81 seconds; p < 0.05). CONCLUSIONS: The saphenous vein from hypertensive patients is less distensible, slower to relax, and more reactive to at least two agonists. These differences could influence the graft's patency and the clinical outcome.

Dynamic cardiomyoplasty: a new approach to assist chronic myocardial failure.

The concept of 'reconstructive cardiac surgery' using a stimulated autologous skeletal muscle has been investigated in this research. Our approach has been to investigate the substitution or reinforcement of a ventricular wall by a contractile tissue. The experiments have demonstrated the feasibility of this technique and the long-term adaptability and adequate electrophysiological properties of the Latissimus Dorsi flap transferred to a heterotopic position over the heart. Long-term biocompatible fatigue resistant muscle stimulation has become possible in experimental and clinical cases as a result of the development of specially designed electrodes and the use of a progressive sequential stimulation protocol to adapt the skeletal muscle to a cardiac support function. Autologous pericardium treated with glutaraldehyde was found to be a suitable material to close the ventricular cavity. Cardiomyoplasty with autologous skeletal muscle to restore ventricular contractility seems to be a valid alternative in addition to current methods of treatment for irreversible myocardial failure.