Samuel Rivers

Limiting ischemic myocardial damage using glucose-insulin-potassium solutions

BACKGROUND This experimental study sought to determine whether the infusion of glucose-insulin-potassium (GIK) solutions to ischemic myocardium during revascularization would decrease myocardial damage. METHODS In 40 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 30 minutes of cardioplegic arrest and 180 minutes of reperfusion. During the periods of coronary occlusion and reperfusion, 10 pigs received GIK (glucose = 300 g/L, insulin = 50 U/L, K+ = 80 mEq/L) through the jugular vein at 1 mL.kg-1.h-1 (GIK-IV group); 10 pigs received GIK through the coronary sinus (GIK-CS group); 5 pigs received GIK through the jugular vein during reperfusion only (GIK-R group); 5 pigs received GIK through the jugular vein 2 hours prior to coronary occlusion and then during the periods of coronary occlusion and reperfusion (GIK-Pre group); and 10 pigs received no GIK (Unmodified group). Ischemic damage was assessed by wall motion scores using two-dimensional echocardiography, changes in myocardial tissue pH, and the area of necrosis in the area of risk. RESULTS Hearts treated with GIK had significantly less tissue acidosis, higher wall motion scores, and the least tissue necrosis (14% +/- 2% GIK-Pre versus 12% +/- 2% GIK-CS versus 16% +/- 2% GIK-IV versus 25% +/- 2% GIK-R versus 73% +/- 4% Unmodified; all, p < 0.05 versus Unmodified). CONCLUSIONS We conclude that a glucose-insulin-potassium solution reduces ischemic myocardial damage during coronary revascularization.

Total complement inhibition: an effective strategy to limit ischemic injury during coronary revascularization on cardiopulmonary bypass.

BACKGROUND Activation of complement during revascularization of ischemic myocardium accentuates myocardial dysfunction. Soluble human complement receptor type 1 (sCR1) is a potent inhibitor of complement, as are heparin-bonded (HB) cardiopulmonary bypass (CPB) circuits. This study sought to determine whether total complement inhibition with the combination of sCR1 and HB-CPB limits damage during the revascularization of ischemic myocardium. METHODS AND RESULTS In 40 pigs, the second and third diagonal coronary arteries were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. In 10 pigs, sCR1 (10 mg/kg) was infused 5 minutes after the onset of coronary occlusion (sCR1), 10 received HB-CPB only (HB-CPB), 10 received sCR1 and HB-CPB (sCR1+HB), and 10 received neither sCR1 or HB-CPB (unmodified). Addition of sCR1 to the HB group resulted in less myocardial tissue acidosis (DeltapH = -0.72+/-0.03 for unmodified; -0.46+/-0.05 for HB; -0.18+/-0.04 for sCR1; -0.13+/-0.01 for sCR1+HB), better recovery of wall motion scores (4 = normal to -1 = dyskinesia; 1.67+/-0.17 for unmodified; 2.80+/-0.08 for HB; 3.35+/-0.10 for sCR1; 3.59+/-0.08 for sCR1+HB), less lung water accumulation (5.46+/-0.28% for unmodified; 2.39+/-0.34% for HB; 1.22+/-0.07% for sCR1; 1.24+/-0.13% for sCR1+HB), and smaller infarct size (area necrosis/area risk = 44.6+/-0.7% for unmodified; 33.2+/-1.9% for HB; 19.0+/-2.4% for sCR1; 20+/-1.0% for sCR1+HB) (P<0.05 versus unmodified; P<0.05 versus unmodified and HB groups). CONCLUSIONS Total complement inhibition with sCR1 and sCR1+HB circuits optimizes recovery during the revascularization of ischemic myocardium.

High tissue affinity angiotensin-converting enzyme inhibitors improve endothelial function and reduce infarct size.

BACKGROUND Angiotensin-converting enzyme (ACE) inhibitors differ in their ability to inhibit tissue ACE. This study was, therefore, undertaken to determine whether high tissue affinity ACE inhibitors would improve endothelial function and thereby decrease tissue necrosis during ischemia. METHODS In a porcine model, the second and third diagonal vessels were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. During the period of coronary occlusion, 10 pigs received enalaprilat (low affinity tissue ACE inhibitor), 0.05 mg/kg intravenously, 10 received quinaprilat (high affinity tissue ACE inhibitor), 10 mg intravenously, and 10 others received no ACE inhibitor. RESULTS Wall motion scores (4, normal, to -1, dyskinesia) were higher in animals treated with ACE inhibitors (3.20+/-0.15 SE enalaprilat versus 3.08+/-0.23 quinaprilat versus 1.52+/-0.07 no ACE; both p < 0.0001 from no ACE). Endothelial-dependent relaxation to bradykinin was best preserved in the quinaprilat-treated hearts (32.1%+/-7.6% enalaprilat versus 65.8%+/-12.6% quinaprilat versus 30.6%+/-10.7% no ACE; p < 0.0001 from no ACE; p < 0.005 from enalaprilat). This was associated with a greater reduction in infarct size: area necrosis/area risk 24.3%+/-0.8% enalaprilat (p < 0.0001 from no ACE) versus 14.3%+/-3.2% quinaprilat (p < 0.0001 from no ACE; p < 0.005 from enalaprilat) versus 40.0%+/-1.7% no ACE. CONCLUSIONS ACE inhibitors with higher affinity to tissue ACE result in better preservation of endothelial function and less tissue necrosis during coronary revascularization.

Role of leukocyte depletion during cardiopulmonary bypass and cardioplegic arrest

BACKGROUND Leukocyte depletion (LD) has been shown to be beneficial during the reperfusion of acutely ischemic myocardium; however, its role during cardiopulmonary bypass (CPB) in hearts protected with blood cardioplegia (BCP) is unknown. This experimental study sought to determine whether LD filters inserted in the CPB circuit before cardioplegic arrest and in the BCP circuit during arrest would decrease ischemic myocardial damage. METHODS In 20 pigs, the second and third diagonal vessels were occluded for 90 minutes, followed by 45 minutes of BCP arrest and 180 minutes of reperfusion on CPB. In 5 pigs, LD filters were inserted in both the CPB and BCP circuits (LD-CPB+BCP). Five pigs had LD during BCP (LD-BCP), 5 pigs had LD during CPB (LD-CPB), and 5 pigs had no LD. Ischemic damage was assessed by wall motion scores using two-dimensional echocardiography and the area of necrosis/area of risk. RESULTS The LD-CPB and LD-CPB+BCP groups had the highest wall motion scores and the lowest area of necrosis/area of risk. The addition of LD to BCP alone did not significantly alter wall motion scores or the area of necrosis/area of risk. CONCLUSION Leukocyte depletion filters significantly reduce ischemic damage during acute surgical revascularization and appear to be most effective when placed in the CPB circuit before cardioplegic arrest.

Soluble Complement Receptor Type I Limits Damage During Revascularization of Ischemic Myocardium

BACKGROUND This study was undertaken to determine whether suppression of complement activation with soluble human complement receptor type I reduces myocardial damage during the revascularization of ischemic myocardium. METHODS In 20 pigs, the second and third diagonal coronary arteries were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. In 10 pigs, soluble human complement receptor type I (10 mg/kg) was infused over 30 minutes before the period of coronary occlusion; 10 other pigs received no soluble human complement receptor type I. Complement activation was measured by total hemolytic complement activity (expressed as a percentage of preischemic values). Ischemic damage was assessed by changes in myocardial tissue pH, wall motion scores (range, 4=normal to -1=dyskinesia), and infarct size (area of necrosis versus area at risk). RESULTS After 180 minutes of reperfusion, hearts treated with soluble human complement receptor type I had significantly less complement activation than nontreated hearts (1.1%+/-0.09% versus 7.8%+/-0.04%, respectively; p < 0.002), less myocardial acidosis (-0.41+/-0.03 versus -0.72+/-0.03, respectively; p < 0.0001), higher wall motion scores (3.1+/-0.09 versus 1.67+/-0.16, respectively; p < 0.0001), and smaller infarct size (24.6%+/-2.0% versus 41%+/-1.3%, respectively; p < 0.0001). CONCLUSIONS Complement inhibition with soluble human complement receptor type I significantly limits ischemic damage during the revascularization of acutely ischemic myocardium.

Superiority of retrograde cardioplegia after acute coronary occlusion

Because antegrade cardioplegia may limit the distribution of cardioplegia beyond a coronary occlusion, this study was undertaken to determine whether retrograde coronary sinus cardioplegia provides superior myocardial protection during revascularization of an acute coronary occlusion. In 20 adult pigs, the second and third diagonal branches were occluded with a snare for 1 1/2 hours. Animals were then placed on cardiopulmonary bypass and underwent 30 minutes of ischemic arrest with multidose, potassium, crystalloid cardioplegia. In 10 animals, the cardioplegia was given antegrade through the aortic root, whereas in 10 others, it was given retrograde through the coronary sinus. After the arrest period, the coronary snares were released and all hearts were reperfused for 3 hours. Postischemic damage in the myocardium beyond the occlusions was assessed by wall motion scores using two-dimensional echocardiography (4 = normal to -1 = dyskinesia), the change in myocardial pH from preischemia, and the area of necrosis/area of risk (histochemical staining). Hearts protected with retrograde coronary sinus cardioplegia had less tissue acidosis (change in pH = 0.08 +/- 0.03 versus 0.41 +/- 0.13; p less than 0.05), higher wall motion scores (2.0 +/- 0.6 versus 1.3 +/- 0.3; not significant), and less myocardial necrosis (43.4% +/- 3.6% versus 73.3% +/- 3.5%; p less than 0.0001). We conclude that retrograde coronary sinus cardioplegia provides more optimal myocardial protection than is possible with antegrade cardioplegia after revascularization of an acute coronary occlusion.

Heparin-Bonded Circuits Decrease Myocardial Ischemic Damage: An Experimental Study

BACKGROUND Heparin-bonded cardiopulmonary bypass circuits reduce complement activation, but their effect on myocardial function is unknown. This study was undertaken to determine whether heparin-bonded circuits reduce myocardial damage during acute surgical revascularization. METHODS In 16 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion with the snares released. During the period of coronary occlusion, all animals were placed on percutaneous bypass followed by standard cardiopulmonary bypass during the periods of cardioplegic arrest and reperfusion. In 8 pigs, heparin-bonded circuits were used, whereas 8 other pigs received nonbonded circuits. RESULTS Animals treated with heparin-bonded circuits had the best preservation of wall motion scores (3.5 +/- 0.3 versus 2.3 +/- 0.2; 4 = normal to -1 = dyskinesis; p < 0.05), least tissue acidosis (change in pH = -0.31 +/- 0.02 versus -0.64 +/- 0.08; p < 0.05), smallest increase in lung H2O (1.7% +/- 0.7% versus 6.1% +/- .5%; p < 0.05), and the lowest area of necrosis/area of risk (20.3% +/- 2.2% versus 40.4% +/- 1.6%; p < 0.05). CONCLUSIONS We conclude that heparin-bonded circuits significantly decrease myocardial ischemic damage during acute surgical revascularization.

Enhanced recovery of ischemic myocardium by combining percutaneous bypass with intraaortic balloon pump support

Although percutaneous bypass (PB) can support the failing myocardium, regional ischemic damage may still occur beyond a coronary occlusion. This study sought to determine whether the addition of intraaortic balloon pump (IABP) support to PB would result in more optimal salvage of ischemic myocardium. In 30 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 30 minutes of cardioplegic arrest and 3 hours of reperfusion with the snares released. During the period of coronary artery occlusion, 10 pigs were placed on PB, 10 pigs received PB plus IABP support, and 10 pigs received no support (the unmodified group). The hearts treated with the combination of PB and IABP support exhibited the highest wall motion scores (3.3 +/- 0.20 for the PB plus IABP group [p < 0.05 from the unmodified group and from the PB group]; versus 1.40 +/- 0.30 for the PB group versus 1.37 +/- 0.33 for the unmodified group), the least tissue acidosis (change in pH, -0.30 +/- 0.2 for the PB plus IABP group [p < 0.05 from the PB group] versus -0.60 +/- 0.10 for the PB group versus -0.41 +/- 0.13 for the unmodified group), and the least area of necrosis (25% +/- 5% for the PB plus IABP group [p < 0.05 from the unmodified group and from the PB group]; versus 43% +/- 2% for the PB group [p < 0.05 from the unmodified group] versus 73% +/- 3% for the unmodified group).(ABSTRACT TRUNCATED AT 250 WORDS)

Improved Distribution of Cardioplegia with Pressure-Controlled Intermittent Coronary Sinus Occlusion

Coronary occlusions may alter the distribution of antegrade cardioplegia and result in ischemic damage. This study was undertaken to determine whether pressure-controlled intermittent coronary sinus occlusion (PICSO) could improve antegrade cardioplegic delivery when coronary occlusions are present. Twenty pigs were subjected to 120 minutes of ischemic arrest with antegrade, multidose, potassium crystalloid cardioplegia. During arrest, the mid-left anterior descending artery was occluded with a snare, which was released on reperfusion. In 10 pigs, a balloon-tipped catheter was placed in the coronary sinus and PICSO was performed during each cardioplegia dose. PICSO-treated hearts had faster arrests (27 +/- 5 versus 102 +/- 21 [SE] seconds; p less than 0.02), as well as lower temperatures (18.4 +/- 1.0 versus 22.0 +/- 1.4 degrees C; p less than 0.05) and higher tissue pH (6.58 +/- 0.09 versus 6.31 +/- 0.09; p less than 0.05) just before aortic unclamping. Postischemic end-diastolic volume was unchanged with PICSO, but it decreased in non-PICSO-treated hearts. PICSO-treated hearts generated a higher postischemic stroke work index (0.70 +/- 0.08 versus 0.38 +/- 0.08 g-m/kg; end-diastolic volume, 60 ml; p less than 0.05). We conclude that PICSO improves cardioplegic distribution, thus reducing ischemic injury.

Pretreatment with angiotensin-converting enzyme inhibitors attenuates ischemia-reperfusion injury

BACKGROUND The Heart Outcomes Prevention Evaluation (HOPE) trial demonstrated that ischemic events are decreased in patients receiving angiotensin-converting enzyme (ACE) inhibitors. This study sought to determine whether pretreatment with ACE inhibitors would attentuate ischemic injury during surgical revascularization of ischemic myocardium. METHODS In a porcine model, the second and third diagonal vessels were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest, and 180 minutes of reperfusion. Ten pigs received quinapril (20 mg p.o. q.d.) for 7 days prior to surgery; 10 others received no-ACE inhibitors. RESULTS Quinapril-treated animals required less cardioversions for ventricular arrhythmias (1.58 +/- 0.40 vs 2.77 +/- 0.22; p < 0.05), had higher wall motion scores assessed by two-dimensional echocardiography (4 = normal to -1 = dyskinesia; 2.11 +/- 0.10 vs 1.50 +/- 0.07; p < 0.05), more complete coronary artery endothelial relaxation to bradykinin (45% +/- 3% vs 7% +/- 4%; p < 0.005), and lower infarct size (24.0% +/- 3.0% vs 40.0% +/- 1.7%; p < 0.0001). CONCLUSIONS ACE inhibition prior to coronary revascularization enhances myocardial protection by decreasing ventricular irritability, improving regional wall motion, lowering infarct size, and preserving endothelial function.