- Email: [email protected]
Myocardial protective effect of captopril cardioplegia against ischaemia and reperfsuion injury in the isolated rabbit heart
MYOCARDIAL PROTECTIVE EFFECT OF CAFI’OPRIL CARDIOPLECIA AGAINST ISCIIAERIIA AND REPERFSUION INJURY IN THE ISOLATED RABBIT HEART XII Shou-cl~un, Liu Feng-ming, *Lnlimer
R D
Department of Anesthesia and Fuwai Hospital, Beijing, PRC *Department of Anaesthetics, Papworth Hospital, Cambridge, England
INTRODUCTION Our previous clinical study showed that the combined use of captopril and cardioplegia may be beneficial during open heart surgery [I]. The myocardial protective effect of captopril cardioplegia was investigated through the recovery of cardiac functions, biochemical changes and ul~rastructural assays in the isolatmi working rabbit heart after hypothermic ischaernic arrest for 3 hours.
AIETiIOD The isolated working rabbit heart preparation which was described in detail by Michio was used [2]. Hearts were randomly divided into 3 groups of 8. Another 3 groups of hearts (8 in each) were arranged for studying the biochemical changes and ultrastructure during the ischaemic period only. In control group (I) the hearts were protected by the modifted St Thomas’ cardioplegic solulion No 1 only, while in Group If and III the cardioplegic solutions contained 2.3 gmol/l and 23 ~molll captopril respectively. The ultrastructural changes in the mihxhondria were evaluated semiquantitatively by Flameng’s score 131. Ethical approval was obtained.
RESULTS The results showed significant improvements in recovery of cardiac function in the 23 ~.lmol/l captopril group compared with the conlrol group after 180 minutes ischaemic arrest at 13°C with repeat cardioplegia every 30 minutes.
P
160TI 140 E lZO I1 ; 100 ;
I c
:
‘lo 20
DISCUSSION The results of the present study show that captopril does significanlly enhance the myocardial protective effect of the modified St Thomas’ cardioplegic solution No 1 against 180 minute global ischaemia and reperfusion injury in the hypothermic isolated rabbit heart. During the working mode of Ihe reperfusion period, both captopril containing cardioplegic solutions could greatly improve the recovery of cardiac function compared with fhe control group. The improvements in coronary flow (CF) and aortic flow (AF) in Group III were most impressive. It is well recognized that the cardiac output (CO) is determined by the preload, afterload, myocardial contractility and heart rate. In all our isolated working hearts, the left ventricular filling pressures and the afterloads were constantly kept at I.96 kPa (20 cm H,O) and 7.84 kPa (80 cm H,O) respectively, and the HR did not increase during reperfusion. Therefore, the increase of CO must be due lo the increase of stroke volume (SV), which wac the contribution of the improvements of +dp/dt max (I 18~33%) and -dp/dt max (I 11+22%). It is obvious that the increase of coronary flow, induced by captopril, was the primary change which may he the basis for the improvement of the cardiac performance. The mechanism of the coronary vasodilatation iuduced by caplopril may be quite complicated. Inhibition of angiotensin production and calecholamine release, activation of prostacycline biosynthesis, enhancement of the activity of EDRF and prevention of bradykinin degradation may play an important role in it.
CONCLUSION global ischaemia and subsequent reperfusion injury. On the one hand captopril may anatagonize.the cytotoxic effect of free radicals to keep lhe inlegrity of cell structures and restore the activities of cell
GO
:
ischaemic arrest.
Captopril cardioplegia appears to protect (he myocardium against
GO
:
The mitochondrial ultrastructure was significantly better preserved in both Captopril groups compared to the control group after 180 minutes
sv Fig.
organelles, and on the other hand, it increases the coronary flow which promotes the resynthesis of high-energy phosphales and fmally promotes the recovery of cardiac performance.
I.
Comparison of the hemodynamic recoveries between the control References 1
Anderson LW, Baek L, Bjarne S, et al: Effect [,I Melhylprednisolone on endotoxaemia and complement activation during cardiac surgery. I Cardiothorac Anesth 1989;3:544-549.
2
Nilsson MD, Kulander L, Nystrom S-O, et al: Endotoxins in cardiopulmonary bypass. J Thorac Cardiovasc Surg 1990;100:777-780.
3
Ghosh S. Latimer RD, Gray B, et al: organ injury.
4 Aller
lschemla
Aller
Reperfuslon
Fig. 2 Milochondrial changes after ischemia and repel-fusion
Endotoxin induced
Crit Care Med 1992 (accepled for publication).
Mesenteric Carter A, Latimer RD. Oduro A, et al: ischaemia and endotoxaemia during cardiopulmonary bypass may cause significant splanchnic injury in transplant patients. J Cardiothorac Anesth 1990:4:53:76.
R D
Department of Anesthesia and Fuwai Hospital, Beijing, PRC *Department of Anaesthetics, Papworth Hospital, Cambridge, England
INTRODUCTION Our previous clinical study showed that the combined use of captopril and cardioplegia may be beneficial during open heart surgery [I]. The myocardial protective effect of captopril cardioplegia was investigated through the recovery of cardiac functions, biochemical changes and ul~rastructural assays in the isolatmi working rabbit heart after hypothermic ischaernic arrest for 3 hours.
AIETiIOD The isolated working rabbit heart preparation which was described in detail by Michio was used [2]. Hearts were randomly divided into 3 groups of 8. Another 3 groups of hearts (8 in each) were arranged for studying the biochemical changes and ultrastructure during the ischaemic period only. In control group (I) the hearts were protected by the modifted St Thomas’ cardioplegic solulion No 1 only, while in Group If and III the cardioplegic solutions contained 2.3 gmol/l and 23 ~molll captopril respectively. The ultrastructural changes in the mihxhondria were evaluated semiquantitatively by Flameng’s score 131. Ethical approval was obtained.
RESULTS The results showed significant improvements in recovery of cardiac function in the 23 ~.lmol/l captopril group compared with the conlrol group after 180 minutes ischaemic arrest at 13°C with repeat cardioplegia every 30 minutes.
P
160TI 140 E lZO I1 ; 100 ;
I c
:
‘lo 20
DISCUSSION The results of the present study show that captopril does significanlly enhance the myocardial protective effect of the modified St Thomas’ cardioplegic solution No 1 against 180 minute global ischaemia and reperfusion injury in the hypothermic isolated rabbit heart. During the working mode of Ihe reperfusion period, both captopril containing cardioplegic solutions could greatly improve the recovery of cardiac function compared with fhe control group. The improvements in coronary flow (CF) and aortic flow (AF) in Group III were most impressive. It is well recognized that the cardiac output (CO) is determined by the preload, afterload, myocardial contractility and heart rate. In all our isolated working hearts, the left ventricular filling pressures and the afterloads were constantly kept at I.96 kPa (20 cm H,O) and 7.84 kPa (80 cm H,O) respectively, and the HR did not increase during reperfusion. Therefore, the increase of CO must be due lo the increase of stroke volume (SV), which wac the contribution of the improvements of +dp/dt max (I 18~33%) and -dp/dt max (I 11+22%). It is obvious that the increase of coronary flow, induced by captopril, was the primary change which may he the basis for the improvement of the cardiac performance. The mechanism of the coronary vasodilatation iuduced by caplopril may be quite complicated. Inhibition of angiotensin production and calecholamine release, activation of prostacycline biosynthesis, enhancement of the activity of EDRF and prevention of bradykinin degradation may play an important role in it.
CONCLUSION global ischaemia and subsequent reperfusion injury. On the one hand captopril may anatagonize.the cytotoxic effect of free radicals to keep lhe inlegrity of cell structures and restore the activities of cell
GO
:
ischaemic arrest.
Captopril cardioplegia appears to protect (he myocardium against
GO
:
The mitochondrial ultrastructure was significantly better preserved in both Captopril groups compared to the control group after 180 minutes
sv Fig.
organelles, and on the other hand, it increases the coronary flow which promotes the resynthesis of high-energy phosphales and fmally promotes the recovery of cardiac performance.
I.
Comparison of the hemodynamic recoveries between the control References 1
Anderson LW, Baek L, Bjarne S, et al: Effect [,I Melhylprednisolone on endotoxaemia and complement activation during cardiac surgery. I Cardiothorac Anesth 1989;3:544-549.
2
Nilsson MD, Kulander L, Nystrom S-O, et al: Endotoxins in cardiopulmonary bypass. J Thorac Cardiovasc Surg 1990;100:777-780.
3
Ghosh S. Latimer RD, Gray B, et al: organ injury.
4 Aller
lschemla
Aller
Reperfuslon
Fig. 2 Milochondrial changes after ischemia and repel-fusion
Endotoxin induced
Crit Care Med 1992 (accepled for publication).
Mesenteric Carter A, Latimer RD. Oduro A, et al: ischaemia and endotoxaemia during cardiopulmonary bypass may cause significant splanchnic injury in transplant patients. J Cardiothorac Anesth 1990:4:53:76.