Comparison of hyperkalemic cardioplegia with altered [CaCl2] and [MgCl2] on [Ca2+]i transients and function after warm global ischemia in isolated hearts.
OBJECTIVE
[MgCl(2)] and [CaCl(2)] may modify the cardioprotective effects of hyperkalemic cardioplegia (CP). We changed [MgCl(2)] and [CaCl(2)] in a CP solution to examine their effects on [Ca(2+)]i transients and cardiac function before and after global normothermic ischemia.


METHODS
After stabilization and loading of indo 1-AM in Kreb's solution (KR), each heart was perfused with either KR or 1 of 4 CP solutions before 37 degrees C, 30 min ischemia followed by reperfusion with KR. The KR solution contained, in mM, 4.5 KCl, 2.4 MgCl(2) and 2.5 CaCl(2); the CP solutions had in addition to 18 KCl: CP 1 (control CP): 2.4 MgCl(2), 2.5 CaCl(2); CP 2: 7.2 MgCl(2), 2.5 CaCl(2); CP 3, 7.2 MgCl(2), 1.25 CaCl(2); CP 4: 2.4 MgCl(2), 1.25 CaCl(2).


RESULTS
In the KR group [Ca(2+)]i markedly increased on early reperfusion while functional return (LVP, dLVP/dt((max and min))) was much reduced; each CP group led to reduced [Ca(2+)]i loading and improved function. The rates of cytosolic Ca(2+) fluxes (d[Ca(2+)]/dt(max) and d[Ca(2+)]/dt(min)) increased significantly compared to baseline in the KR group, but were mostly suppressed in the CP groups, and d[Ca(2+)]/dt(min) was lower after CP 4 compared to CP 1 on reperfusion. At 60 min reperfusion, LVP area to [Ca(2+)] area and cardiac efficiency to phasic [Ca(2+)] relationships were shifted after KR, but not after CP 1-4. With similar functional recovery, [Ca(2+)] transient and [Ca(2+)] area were significantly lower after CP 4 than after CP 1.


CONCLUSIONS
Increasing [MgCl(2)] (CP 2 and 3) did not improve cardiac function or reduce Ca(2+) transients on reperfusion better than the other CP groups, but reducing [CaCl(2)] (CP 3 and 4) was more effective in reducing [Ca(2+)] transients on reperfusion after global ischemia.
Camara
A K S
AK
Anesthesiology Research Laboratories, Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Chen
Q
Q
An
J
J
Novalija
E
E
Riess
M L
ML
Rhodes
S S
SS
Stowe
D F
DF
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000502:physiology; D002122:Calcium Chloride / Q000494:pharmacology / Q000627:therapeutic use*; D002314:Cardioplegic Solutions / Q000737:chemistry / Q000627:therapeutic use; D003326:Coronary Circulation / Q000187:drug effects; D003600:Cytosol / Q000737:chemistry / Q000187:drug effects; D003971:Diastole / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D006324:Heart Arrest, Induced / Q000379:methods; D006339:Heart Rate / Q000187:drug effects; D007552:Isotonic Solutions / Q000737:chemistry / Q000627:therapeutic use; D015636:Magnesium Chloride / Q000494:pharmacology / Q000627:therapeutic use*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology / Q000627:therapeutic use; D013599:Systole / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects*
D002314:Cardioplegic Solutions; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D015636:Magnesium Chloride; D011189:Potassium Chloride; D002122:Calcium Chloride; D002118:Calcium