Modulation of severity of reperfusion stunning in the isolated rat heart by agents altering calcium flux at onset of reperfusion.
The present study tested the hypothesis that a reduction in calcium flux across the sarcolemma or the sarcoplasmic reticulum at the onset of reperfusion could attenuate subsequent mechanical "stunning" (postischemic myocardial dysfunction). The isolated working rat heart was subjected to 20 minutes of total global ischemia, reperfused in the Langendorff mode for 5 minutes, and then made to work again for 10 minutes. During the early reperfusion period (first 2 minutes), the effects of agents thought to increase cytosolic calcium (high external calcium [modified Tyrode's solution replaced Krebs-Henseleit buffer as the perfusate], isoproterenol, forskolin, and Bay K 8644) were tested. All these interventions worsened stunning. The cardiac output (CO) of control hearts recovered to 74.7 +/- 3.4%, whereas recovery was 56.3 +/- 3.7% (p less than 0.05) for high calcium (10 mM), 53.4 +/- 3.6% (p less than 0.05) for isoproterenol, 43.4 +/- 4.1% (p less than 0.05) for Bay K 8644, and 62.7 +/- 2.4% (p less than 0.002) for forskolin. Interventions aimed at limiting calcium flux during early reperfusion, such as reperfusion with a low extracellular calcium or the addition of ryanodine (3 x 10(-9) M), nisoldipine (10(-8) M), or the inorganic blockers Mn2+ (2 mM) or Mg2+ (16 mM), were also tested. Low extracellular calcium (0.75 mM) improved CO to 91.8 +/- 0.8% (p less than 0.05). Reperfusion with ryanodine and nisoldipine gave CO recoveries of 103.6 +/- 1.8% (p less than 0.002) and 99.0 +/- 2.8% (p less than 0.002), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
du Toit
E F
EF
Department of Medicine, Groote Schuur Hospital, Cape Town, South Africa.
Opie
L H
LH
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology*; D015737:Nisoldipine / Q000494:pharmacology; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D012433:Ryanodine; D015737:Nisoldipine; D002118:Calcium