Effects of nisoldipine on recovery of coronary blood flow, sarcoplasmic reticulum function and other biochemical parameters in post-ischaemic porcine myocardium.
The effects of nisoldipine (0.1 micrograms/kg/min; n = 9) or its solvent (n = 9) were studied in pigs, in which left anterior descending coronary artery (LADCA) blood flow in both groups was reduced to 20% of baseline for 60 min and reperfused for 2 hr. Infusions were started at 30 min of ischaemia and lasted throughout reperfusion. In both groups, flow reduction abolished regional contractile function and caused similar decreases in the level of creatine phosphate (CP; by 70%) and the energy charge (from 0.91 to 0.69), mean arterial blood pressure (by 25%), LVdP/dtmax (by 30%) and cardiac output (by 30%). During ischaemia LADCA blood flow slightly increased (from 14 +/- 8 to 24 +/- 6 mL/min/100 g; P less than 0.05) in the nisoldipine-treated animals, resulting in an increase in CP to 91 +/- 24% of baseline and preventing further decreases in energy charge, as observed in the solvent-treated animals. After 2 hr of reperfusion in neither group return of contractile function of the post-ischaemic myocardium was observed. Post-ischaemic blood flow in the nisoldipine-treated pigs increased from 24 +/- 6 mL/min/100 g to 76 +/- 14 mL/min/100 g and from 19 +/- 6 mL/min/100 g to 41 +/- 6 ml/min/100 g in the solvent-treated animals (P less than 0.05) after 2 hr of reperfusion. Myocardial work was significantly higher in the nisoldipine-treated animals (111 +/- 15 mmHg.L/min as compared to 69 +/- 14 mmHg.L/min in the solvent-treated pigs after 2 hr of ischaemia). The energy charge of the post-ischaemic myocardium was similar for both groups (0.84 +/- 0.02 for the nisoldipine-treated and 0.83 +/- 0.03 for the solvent-treated animals). The rate of sarcoplasmic reticular Ca2+ uptake of the non-ischaemic segment of the nisoldipine-treated animals was 61% higher (P less than 0.05) than that of the solvent-treated animals. In the post-ischaemic myocardium similar rates of Ca2+ uptake were found in both groups, but the activities were markedly lower as compared to the non-ischaemic myocardium. It is concluded that nisoldipine increases blood flow during reperfusion, which may have been caused by coronary vasodilatation. However, attenuation of the "no-reflow" phenomenon also contributed, since more rapid rephosphorylation of ADP leading to an increase in CP during ischaemia may have preserved jeopardized cells. Moreover, nisoldipine increases the sarcoplasmic reticular Ca2+ pump activity independent of ischaemia, which may have contributed in reducing the Ca2+ overload.
Sassen
L M
LM
Laboratory for Experimental Cardiology, Thoraxcenter, Rotterdam, The Netherlands.
Bezstarosti
K
K
Verdouw
P D
PD
Lamers
J M
JM
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000503:physiopathology; D015425:Myocardial Reperfusion; D015737:Nisoldipine / Q000494:pharmacology*; D010725:Phosphocreatine / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D015737:Nisoldipine; D010725:Phosphocreatine; D010761:Phosphorus Radioisotopes; D000099211:Phospholamban