Effects of magnesium cardioplegia on regulation of the porcine coronary circulation.
We compared the effect of hypermagnesium and hyperkalemic crystalloid cardioplegia on beta-adrenoceptor-mediated and endothelium-dependent relaxation and myogenic responses of coronary arterioles. Pigs were placed on cardiopulmonary bypass. Hearts were arrested with cold hypermagnesium (25 mM Mg2+, hyper-Mg, n = 12) or hyperkalemic (25 mM K+, hyper-K, n = 12) crystalloid cardioplegia for 1 hr. Hearts of selected pigs (n = 6 in each group) were then reperfused for 1 hr. In vitro relaxation responses of acetylcholine-pre-contracted arterioles were studied in a pressurized no-flow state with video-microscopy. Relaxation of pre-contracted coronary microvessels (70-150 microns) to isoproterenol (beta-adrenergic agonist) and forskolin (adenylate cyclase activator) was preserved after cardioplegia using a hyper-Mg solution. In contrast, responses were impaired to isoproterenol [P < 0.01 (two-factor ANOVA) vs. controls, n = 6] and forskolin (P < 0.01) after hyper-K cardioplegia. After 1 hr of reperfusion, relaxation responses to isoproterenol and forskolin were partially recovered. Hyper-Mg cardioplegia and post-cardioplegic reperfusion did not affect receptor-mediated endothelium-dependent relaxation to ADP, non-receptor-mediated endothelium-dependent relaxation to A23187, and endothelium-independent relaxation to nitroprusside. However, responses to ADP (P < 0.01) and A23187 (P < 0.05) were selectively impaired after hyper-K cardioplegia. Myogenic contraction was impaired after either hyper-Mg or hyper-K cardioplegia. Left ventricular systolic pressure, coronary blood flow, and +dP/dt were similar after hyper-Mg or hyper-K cardioplegia. These results suggest that hyper-Mg cardioplegia is superior to hyper-K cardioplegia in terms of preserving beta-adrenoceptor-mediated and endothelium-dependent regulation of the coronary microcirculation, yet it has minimal if any additional beneficial effect on preserving myogenic responses or myocardial contractile function.
Tofukuji
M
M
Department of Surgery of Beth Israel-Deaconess Medical Center, Boston, Massachusetts, USA.
Stamler
A
A
Li
J
J
Franklin
A
A
Wang
S Y
SY
Hariawala
M D
MD
Sellke
F W
FW
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D000001:Calcimycin / Q000494:pharmacology; D002314:Cardioplegic Solutions / Q000737:chemistry*; D003080:Cold Temperature; D005576:Colforsin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D002314:Cardioplegic Solutions; D009599:Nitroprusside; D005576:Colforsin; D000001:Calcimycin; D008274:Magnesium; D007545:Isoproterenol