Myocardial free-radical injury after cardioplegia

Although cold blood cardioplegia provides excellent myocardial protection for elective coronary bypass surgery, myocardial metabolic recovery is delayed postoperatively, perhaps because of free-radical injury during reperfusion. To assess free-radical reperfusion injury, we measured the products of lipid peroxidation and the cardiac concentrations of alpha tocopherol in 10 patients undergoing elective surgical revascularization. Arterial and coronary sinus blood measurements revealed a delayed recovery of myocardial oxygen consumption and lactate utilization and the myocardial release of conjugated dienes (chemical signatures of free-radical injury) at 3 and 60 minutes after reperfusion. In addition, myocardial concentrations of alpha tocopherol decreased after reperfusion, suggesting consumption of the major membrane antioxidant. These results support the hypothesis that oxygen-derived free radicals contribute to myocardial injury after cardioplegic arrest and that antioxidant therapy should improve myocardial protection.Peer reviewed: YesNRC publication: Ye

Dipyridamole reduced myocardial platelet and leukocyte deposition following ischemia and cardioplegia

Urgent coronary revascularization for acute myocardial ischemia results in an increased mortality and morbidity. Deposition of activated platelets and leukocytes into the ischemic myocardium during reperfusion may augment perioperative ischemic injury. Dipyridamole reduces platelet activation and may reduce myocardial deposition and prevent ischemic injury during reperfusion. The effects of dipyridamole on myocardial platelet and leukocyte deposition were evaluated in a canine model of acute regional myocardial ischemia with reperfusion during cardioplegia on cardiopulmonary bypass. Eight dogs underwent left anterior descending (LAD) coronary artery ligation for 45 min followed by cardiopulmonary bypass and release of the ligature during 60 min of cold crystalloid cardioplegic arrest to stimulate urgent revascularization. Four dogs were randomized to receive an infusion of dipyridamole perioperatively (50 mg/hr) and 4 dogs served as controls. Autologous platelets were labeled with 111In, leukocytes with 99mTc, and erythrocytes with 51Cr. The labeled cells were infused immediately after cross-clamp release and myocardial biopsies were obtained at 10, 20, 30, and 60 min of reperfusion. Platelets were deposited in the myocardium during reperfusion and four times more platelets were found in the LAD region than the circumflex region. Leukocyte deposition was similar in the LAD and circumflex regions. Dipyridamole reduced both platelet and leukocyte deposition and the reduction was greater in the LAD than in the circumflex region. Myocardial platelet and leukocyte deposition was found after regional ischemia, cardioplegia, and cardiopulmonary bypass. Dipyridamole reduced myocardial platelet and leukocyte deposition and may reduce perioperative ischemic injury

Double deprotonation of ruthenium(II) cations containing 1,2-dimethyl-substituted η6-arenes. Protonation of the resulting exo-coordinated (o-xylylene)ruthenium(0) complexes and X-ray crystal structures of the agostic (η3-pentamethylbenzyl)ruthenium(II)

Treatment of the various ruthenium(II) salts [Ru(ONO2)(eta-6-1,2-dimethylarene)L2]NO3 and [Ru(O2CCF3)(eta-6-1,2-dimethylarene)L2]PF6 with KO-t-Bu or (Me3Si)2NNa in the presence of a ligand L' gives o-xylylene (o-quinodimethane) complexes of zerovalent ruthenium, i.e. Ru{eta-4-(CH2)2C6Me4}L2L' (L = L' = PMe2Ph, P(CD3)2Ph, PMePh2, P(OMe)3, P(OCH2)3CMe; L2 = Ph2PCH2CH2PPh2, L' = PMe2Ph; L2 = (Z)-Ph2PCH=CHPPh2, L' = PMe2Ph, P(CD3)2Ph), Ru{eta-4-(CH2)2C6H2Me2}L2L' (L = L' = PMe2Ph, PMePh2), and Ru{eta-4-(CH2)2C6H4}(PMe2Ph)3, in good to moderate yields. In all cases the o-xylylene group is coordinated through its exo pair of double bonds. The reactions are proposed to proceed via the undetected intermediates Ru(o-xylylene)L2 (L = monodentate P-donor ligand, L2 = bidentate P-donor ligand) in which the ruthenium atom can migrate from the endo to the exo pair of double bonds before ligand L' attacks. On treatment with HPF6, Ru{eta-4-(CH2)2C6Me4}L2L' and Ru(eta-4-(CH2)2C6H4}(PMe2Ph)3 give (eta-3-benzyl)ruthenium(II) salts [Ru{eta-3-(HCH2)(CH2)C6Me4}L2L']PF6 (L = Ph2PCH2CH2PPh2, L' = PMe2Ph (1); L = (Z)-Ph2PCH=CHPPh2, L' = PMe2Ph (2), P(CD3)2Ph (2a); L = L' = PMe2Ph (3), P(CD3)2Ph (3a)) and [Ru{eta-3-(HCH2)-(CH2)C6H4}(PMe2Ph)3]PF6 (4) in which the added proton bridges the metal atom and a terminal methylene group. Crystals of 2 are monoclinic, space group P2(1)/n, with a = 18.88.4 (3) angstrom, b = 18.612 (3) angstrom, c = 12.361 (1) angstrom, beta = 90.40 (1)-degrees, and Z = 4; those of 3 are monoclinic, space group C2/c, with a = 21.220 (8) angstrom, b = 23.412 (10) angstrom, c = 18.580 (7) angstrom, beta = 126.05 (1)-degrees, and Z = 8. The structures were solved by heavy-atom methods and refined by least-squares analysis to R = 0.042 and R(w) = 0.053 for 5787 independent reflections (I greater-than-or-equal-to 3-sigma) (2) and R = 0.053 and R(w) = 0.076 for 5832 independent reflections (I > 3-sigma) (3). Both cations contain a ruthenium atom coordinated in a distorted-octahedral arrangement by a eta-3-pentamethylbenzyl group, which occupies two sites, three phosphorus atoms, and an agostic methyl hydrogen atom that has been directly located in 2 but not 3. The eta-3-benzyl interaction in 2 shows the usual asymmetry, the shortest Ru-C bond being to the terminal CH2 group (Ru-C(22) = 2.164 (5) angstrom, Ru-C(2) = 2.342 (4) angstrom, Ru-C(1) = 2.358 (4) angstrom). The metrical parameters defining the agostic Ru-H-CH2 interaction in 2 are r(Ru-C) = 2.416 (5) angstrom, r(Ru-H) = 1.92 (4) angstrom, r(C-H) = 1.01 (5) angstrom, and angle C-H-Ru = 107 (3)-degrees. The distances from ruthenium to the terminal carbon atoms in 3 (Ru-C(11) = 2.333 (9) angstrom, Ru-C(22) = 2.283 (10) angstrom) are almost equal within experimental error, in contrast with the corresponding distances in 2, and indicate that the solid-state structure of 3 is an average in which either C(11) or C(22) is protonated. Variable-temperature NMR (H-1, P-31) spectra of complexes 1, 2, 2a, 3, 3a, and 4 show these molecules to be fluxional as a consequence of three processes: (1) reversible Ru-H (agostic) bond breaking, which cannot be frozen out, even at -100-degrees-C; (2) reversible eta-3 reversible eta-1 interconversions of the benzyl group, for which the estimated DELTA-G(double dagger) values are ca. 13 kcal/mol at 303 K for 2 and ca