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Byline: Bernard L Lopez, Jack W Snyder, Dale S Birenbaum, Xin-liang Ma Abstract: Study Hypothesis: Previous studies have suggested that N-Acetylcysteine (NAC) may confer additional protection in acetaminophen (APAP) overdose by improving hepatic microcirculation. We hypothesize that NAC enhances release of nitric oxide (NO) from the vasculature. Methods: Sprague-Dawley rat superior mesenteric artery rings were suspended in oxygenated Krebs-Henseleit tissue baths and contracted with U-46619 (a thromboxane A.sub.2 -mimetic). In part 1, the effect of NAC on endothelial cell (EC) release of NO was assessed by measurement of vasorelaxation induced by acetylcholine (ACh, an EC-dependent vasorelaxor) in the presence and absence of NAC. In part 2, the effect of glutathione (a major component of NAC hepatoprotection) was examined by measuring ACh-induced vasorelaxation in rings from rats treated with l-buthionine sulfoxamine (BSO, a glutathione synthesis inhibitor). Data were analyzed by repeated-measures ANOVA. Results: Addition of 15 to 30 mmol/L NAC after ring contraction had no direct vasodilatory effect. By contrast, pretreatment of rings with NAC (15 mmol/L) enhanced vasorelaxation induced by ACh (95.0%[+ or -]7.9% versus 62.3%[+ or -]7.6% for control; ACh dose, 1 [mu]mol/L; P Article History: Received 4 November 1997; Revised 13 March 1998; Accepted 9 April 1998 Article Note: (footnote) [star] From the Division of Emergency Medicine, Department of Surgery, Jefferson Medical College, Philadelphia, PA., [star][star] Reprint no. 47/1/92815 , a Address for reprints: Bernard L Lopez, MD, Jefferson Medical College, Division of Emergency Medicine, 1020 Walnut Street, Philadelphia, PA 19107, E-mail lopezb@jeflin.tju.edu

Byline: Hiroki Sato, Zhi-Qing Zhao, James E. Jordan, James C. Todd, Robert D. Riley, C.Spencer Taft, John W. Hammon Jr, Ping Li, Xin-liang Ma, J. Vinten-Johansen Abstract: Ischemia-reperfusion damages endothelium and impairs basal production of nitric oxide. Basally released nitric oxide is cardioprotective by its inhibition of neutrophil activities. Loss of endogenous nitric oxide with endothelial injury may occur during two phases: cardioplegic ischemia and reperfusion (aortic declamping). This study tested the hypothesis that inhibition of endogenously released nitric oxide in hearts subjected to regional ischemia, cardioplegic arrest, and reperfusion (1) restricts endogenous cardioprotection and permits neutrophil-mediated damage and (2) expresses damage during the reperfusion phase. l-Nitro-arginine was used to block basal nitric oxide production. In 22 anesthetized dogs, the left anterior descending artery was ligated for 90 minutes followed by 1 hour of arrest with cold multidose (every 20 minutes) blood cardioplegia. Dogs were divided into three groups: the first group received standard unsupplemented blood cardioplegia (group 1, n = 8), in the second group l-nitro-arginine was administered as an additive to blood cardioplegic solution (1 mmol) and as an infusion during reperfusion (34 mg/kg) (group 2, n = 7), and in the third group l-nitro-arginine was administered only at reperfusion (group 3, n = 7). The ligature was released during the second infusion of cardioplegic solution. Infarct size (triphenyltetrazolium chloride) was increased in group 3 (l-nitro-arginine only at reperfusion) compared with that in group 1 (standard blood cardioplegia) (49% [+ or -] 6% vs 34% [+ or -] 2%, respectively), but was not further extended in group 2 (l-nitro-arginine as an additive to blood cardioplegic solution and at reperfusion) (56% [+ or -] 3%, p > 0.05 vs group 3), which suggests primarily a reperfusion process. Polymorphonuclear neutrophil-specific myeloperoxidase activity in the area at risk was elevated comparably in groups 2 and 3 (group 2: 2.9 [+ or -] 0.5 units/gm tissue, p = 0.06 vs group 1; group 3: 3.9 [+ or -] 1.0 units/gm tissue, p < 0.05 vs group 1) compared with that in the standard blood cardioplegia group (1.7 [+ or -] 0.3 units/gm tissue), suggesting polymorphonuclear neutrophil accumulation occurs primarily during reperfusion. Polymorphonuclear neutrophil adherence in ischemic-reperfused left anterior descending artery segments was comparably greater in group 2 (l-nitro-arginine as an additive to blood cardioplegic solution and at reperfusion: 195 [+ or -] 21 polymorphonuclear neutrophils/mm.sup.2 of artery, p < 0.05 vs group 1) and group 3 (l-nitro-arginine only at reperfusion: 224 [+ or -] 20 polymorphonuclear neutrophils/mm.sup.2 of artery, p < 0.05 vs group 1) relative to that in group 1(108 [+ or -] 19 polymorphonuclear neutrophils/mm.sup.2 of artery). There was no significant adherence to nonischemic circumflex arteries. We conclude that blockade of endogenous nitric oxide augments postischemic injury mediated by polymorphonuclear neutrophils, and this damage is expressed primarily during the reperfusion phase. (J Thorac Cardiovasc Surg 1997;113:399-409) Article History: Received 6 May 1996; Revised 26 June 1996; Revised 10 September 1996; Accepted 12 September 1996 Article Note: (footnote) [star] From the Departments of Cardiothoracic Surgerya and Physiology/Pharmacologyb and the Hypertension Center,c Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, N.C., and the Department of Emergency Medicine,d Jefferson Medical College, Philadelphia, Pa., [star][star] Supported in part by grant HL46179 from the National Heart, Lung, and Blood Institute of the National Institutes of Health., a Read at the Seventy-sixth Annual Meeting of The American Association for Thoracic Surgery, San Diego, Calif., April 28-May 1, 1996., aa Address for reprints: Jakob Vinten-Johansen, PhD, The Cardiothoracic Research Laboratory, Department of Cardiothoracic Surgery, Carlyle Fraser Heart Center of Emory University, 550 W. Peachtree St. NE, Atlanta, GA 30365-2225., acents 0022-5223/97 $5.00 + 0 12/6/78033

Byline: Asatoshi Mizuno, Rufus Baretti, Gerald D. Buckberg, Helen H. Young, Jakob Vinten-Johansen, Xin-Liang Ma, Louis J. Ignarro Abstract: Ischemia and reperfusion may damage myocytes and endothelium in jeopardized hearts. This study tested whether (1) endothelial dysfunction (reduced nitric oxide release) exists despite good contractile performance and (2) supplementation of blood cardioplegic solution with nitric oxide precursor l-arginine augments nitric oxide and restores endothelial function. Among 30 Yorkshire-Duroc pigs, 6 received standard glutamate/aspartate blood cardioplegic solution without global ischemia. Twenty-four underwent 20 minutes of 37[degrees] C global ischemia. Six received normal blood reperfusion. In 18, the aortic clamp remained in place 30 more minutes and all received 3 infusions of blood cardioplegic solution. In 6, the blood cardioplegic solution was unaltered; in 6, the blood cardioplegic solution contained l-arginine (a nitric oxide precursor) at 2 mmol/L; in 6, the blood cardioplegic solution contained the nitric oxide synthase inhibitor l-nitro arginine methyl ester (l-NAME) at 1 mmol/L. Complete contractile and endothelial recovery occurred without ischemia. In jeopardized hearts, complete systolic recovery followed infusion of blood cardioplegic solution and of blood cardioplegic solution plus l-arginine. Conversely, contractility recovered approximately 40% after infusion of normal blood and blood cardioplegic solution plus l-NAME. Postischemic nitric oxide production fell 50% in the groups that received blood cardioplegic solution and blood cardioplegic solution plus l-NAME but was increased in the group that received blood cardioplegic solution l-arginine. In vivo endothelium-dependent vasodilator responses to acetylcholine recovered 75% [+ or -] 5% of baseline in the blood cardioplegic solution plus l-arginine group, but less than 20% of baseline in other jeopardized hearts. Endothelium-independent smooth muscle responses to sodium nitroprusside were relatively unaltered. Myeloperoxidase activity (neutrophil accumulation) was similar in the blood cardioplegic solution (without ischemia) and blood cardioplegic solution plus l-arginine groups (0.01 [+ or -] 0.002 vs 0.013 [+ or -] 0.003 [mu]g/gm tissue). Myeloperoxidase activity was raised substantially to 0.033 [+ or -] 0.002 [mu]g/gm after exposure to normal blood and to 0.025 [+ or -] 0.003 [mu]g/gm after infusion of blood cardioplegic solution and was highest at 0.053 [+ or -] 0.01 [mu]g/gm with exposure to blood cardioplegic solution plus l-NAME in jeopardized hearts. The discrepancy between contractile recovery and endothelial dysfunction in jeopardized muscle can be reversed by adding l-arginine to blood cardioplegic solution. (J Thorac Cardiovasc Surg 1997;113:379-89) Article History: Received 22 May 1996; Revised 6 August 1996; Revised 30 August 1996; Accepted 9 September 1996 Article Note: (footnote) [star] Rufus Baretti was supported in full by the Deutsche Forschungsgemeinschaft (German Research Foundation)., [star][star] Read at the Seventy-sixth Annual Meeting of The American Association for Thoracic Surgery, San Diego, Calif., April 28-May 1, 1996., a Address for reprints: Gerald D. Buckberg, MD, UCLA School of Medicine, Division of Cardiothoracic Surgery, Room B2-375 CHS, 10833 Le Conte Ave., Los Angeles, CA 90095-1741., aa 0022-5223/97 $5.00 + 0 12/6/77854

ABSTRACT In order to determine the behavior of thick-wall cold-rolled steel sections with square and rectangular hollow cross-section, experiments concerning materials properties of the flat coupons, corner coupons, parent plate [...]