Continuous determination of extracellular space and changes of K+, Na+, Ca2+, and H+ during global ischaemia in isolated rat hearts

SummaryPlatelets activated during experimental acute myocardial infarction (AMI) contribute to myocardial injury. This study aimed to investigate whether platelets from patients with AMI increase myocardial injury after ischaemia and reperfusion in isolated rat hearts and the modification of this effect by the P2Y12 receptor antagonist cangrelor and the glycoprotein IIb/IIIa receptor blocker abciximab. Isolated rat hearts were subjected to 40 minutes of global ischaemia and 60 minutes of reperfusion. Hearts (four simultaneous experiments per patient) were infused with platelets from nine AMI patients (seven thrombolysed, all on aspirin), untreated or incubated with 10 μM cangrelor or 5 μg/ml abciximab. Control experiments were performed using platelets from healthy volunteers and platelet-poor plasma. P-selectin expression on isolated platelets was higher in AMI patients than in controls and was not modified by the treatments. Control platelets or platelet-poor plasma did mild or no harm. In contrast, platelets from AMI patients significantly augmented myocardial injury, as demonstrated by worse left ventricular (LV) developed pressure, higher maximal LV end-diastolic pressure and coronary resistance, and greater lactate dehydrogenase release and infarct size. Both cangrelor and abciximab greatly attenuated these effects. In conclusion, activated platelets from AMI patients increase myocardial injury after ischaemia and reperfusion, and cangrelor and abciximab attenuate this effect. The results support the notion that very early antiplatelet treatment might reduce infarct size by direct effects on reperfused myocardium in these patients.

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Effects of acidic reperfusion on arrhythmias and Na(+)-K(+)-ATPase activity in regionally ischemic rat hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.270.3.h957 ◽

1996 ◽

Vol 270 (3) ◽

pp. H957-H964 ◽

Cited By ~ 5

Author(s):

M. Avkiran ◽

C. Ibuki ◽

Y. Shimada ◽

P. S. Haddock

Keyword(s):

Atpase Activity ◽

Enhanced Recovery ◽

Left Ventricular ◽

Control Group ◽

Protective Mechanism ◽

Acidic Ph ◽

Rat Hearts ◽

Left And Right ◽

Isolated Rat

We studied the effects of acidic reperfusion on 1) the incidence of ventricular fibrillation (VF) and 2) sarcolemmal Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity. Isolated rat hearts (n = 12/group) were subjected to independent perfusion (15 min) of left and right coronary beds with pH 7.4 buffer followed by zero-flow ischemia (10 min) of the former bed. This was then reperfused for 5 min, with acidic (pH 6.6) buffer for the first 0 (control), 0.5,1,2, or 4 min and with pH 7.4 buffer thereafter. In the control group, 92% of hearts developed VF within 20 s of reperfusion and remained in VF. In the 0.5-, 1-, 2-, and 4-min acidic reperfusion groups, only 17, 17, 42, and 25% of hearts (P < 0.05 vs. control for all groups), respectively, exhibited VF during acidic reperfusion. However, on switching to pH 7.4, VF occurred in a further 50, 58, 0, and 0% of hearts, respectively; thus the overall incidences of VF were 67, 75, 42 (P < 0.05 vs. control), and 25% (P < 0.05 vs. control), respectively. Additional hearts (n = 8/group) were used for cytochemical determination of sarcolemmal Na(+)-K(+)-ATPase activity in both the ischemic/reperfused left ventricular (LV) and the nonischemic right ventricular (RV) free walls. Ischemia (10 min) reduced LV Na2(+)-K(+)-ATPase activity from 110 +/- 8 to 25 +/- 3% of the RV value. After 0.5, 1, 2, 3, and 4 min of acidic reperfusion, LV Na(+)-K(+)-ATPase activity was 24 +/- 3, 29 +/- 3, 37 +/- 5, 55 +/- 6, and 70 +/- 4, respectively (P < 0.05 vs. 10-min ischemia). No significant recovery of LV Na(+)-K(+)-ATPase activity occurred following up to 4 min of pH 7.4 reperfusion. In conclusion, 1) at least 2 min of acidic reperfusion is required to achieve sustained protection against VF and 2) the protective mechanism may involve enhanced recovery of Na(+)-K(+)-ATPase activity as well as inhibition of Na+ influx.

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The effect of adrenomedullin, amylin fragment 8-37 and calcitonin generelated peptide on contractile force, heart rate and coronary perfusion pressure in isolated rat hearts

Acta Physiologica Hungarica ◽

10.1556/aphysiol.90.2003.2.6 ◽

2003 ◽

Vol 90 (2) ◽

pp. 133-146 ◽

Cited By ~ 10

Author(s):

Z Kaygısız ◽

N Erkasap ◽

R Uyar ◽

S Kabadere ◽

TE Kabadere ◽

...

Keyword(s):

Heart Rate ◽

Perfusion Pressure ◽

Coronary Perfusion Pressure ◽

Contractile Force ◽

Coronary Perfusion ◽

Rat Hearts ◽

Isolated Rat

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Independent dual perfusion of left and right coronary arteries in isolated rat hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.261.6.h2082 ◽

1991 ◽

Vol 261 (6) ◽

pp. H2082-H2090 ◽

Cited By ~ 4

Author(s):

M. Avkiran ◽

M. J. Curtis

Keyword(s):

High Energy ◽

Low Flow ◽

Blue Dye ◽

Ischemia And Reperfusion ◽

Langendorff Preparation ◽

Rat Hearts ◽

Left And Right ◽

Conventional Models ◽

Aortic Cannula ◽

Isolated Rat

A novel dual lumen aortic cannula was designed and constructed to permit independent perfusion of left and right coronary beds in isolated rat hearts without necessitating the cannulation of individual arteries. Stability of the dual-perfusion preparation was shown to be similar to that of the conventional Langendorff preparation, in terms of coronary flow, heart rate, and high-energy phosphate content. The independence of left and right perfusion beds was confirmed by unilateral infusion of disulfine blue dye and spectrophotometric detection of the dye in ventricular homogenates. Transient cessation of flow to the left coronary bed resulted in severe ventricular arrhythmias upon reperfusion, as in conventional models of regional ischemia and reperfusion. The dual-perfusion model is technically undemanding, reproducible, inexpensive, and can be used in several species. It enables studies with 1) regional low flow ischemia, 2) regional zero-flow ischemia without coronary ligation (with attendant damage to vasculature), 3) selective application of drugs or interventions to the ischemic-reperfused zone, and 4) selective application of components of ischemia and reperfusion to a site anatomically relevant to ischemic heart disease.

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