Devin C Flaherty

Pyruvate-fortified cardioplegia evokes myocardial erythropoietin signaling in swine undergoing cardiopulmonary bypass.

Pyruvate-fortified cardioplegia protects myocardium and hastens postsurgical recovery of patients undergoing cardiopulmonary bypass (CPB). Pyruvate reportedly suppresses degradation of the alpha-subunit of hypoxia-inducible factor-1 (HIF-1), an activator of the gene encoding the cardioprotective cytokine erythropoietin (EPO). This study tested the hypothesis that pyruvate-enriched cardioplegia evoked EPO expression and mobilized EPO signaling mechanisms in myocardium. Hearts of pigs maintained on CPB were arrested for 60 min with 4:1 blood-crystalloid cardioplegia. The crystalloid component contained 188 mM glucose + or - 24 mM pyruvate. After 30-min cardiac reperfusion with cardioplegia-free blood, the pigs were weaned from CPB. Left ventricular myocardium was sampled 4 h after CPB for immunoblot assessment of HIF-1alpha, EPO and its receptor, the signaling kinases Akt and ERK, and endothelial nitric oxide synthase (eNOS), an effector of EPO signaling. Pyruvate-fortified cardioplegia stabilized arterial pressure post-CPB, induced myocardial EPO mRNA expression, and increased HIF-1alpha, EPO, and EPO-R protein contents by 60, 58, and 123%, respectively, vs. control cardioplegia (P < 0.05). Pyruvate cardioplegia also increased ERK phosphorylation by 61 and 118%, respectively, vs. control cardioplegia-treated and non-CPB sham myocardium (P < 0.01), but did not alter Akt phosphorylation. Nitric oxide synthase (NOS) activity and eNOS content fell 32% following control CPB vs. sham, but pyruvate cardioplegia prevented these declines, yielding 49 and 80% greater NOS activity and eNOS content vs. respective control values (P < 0.01). Pyruvate-fortified cardioplegia induced myocardial EPO expression and mobilized the EPO-ERK-eNOS mechanism. By stabilizing HIF-1alpha, pyruvate-fortified cardioplegia may evoke sustained activation of EPOs cardioprotective signaling cascade in myocardium.

Pyruvate-enriched cardioplegia suppresses cardiopulmonary bypass-induced myocardial inflammation.

BACKGROUND Cardiopulmonary bypass-induced oxidative stress initiates inflammation that can damage the myocardium. This study tested whether cardioplegia enriched with the intermediary metabolite and antioxidant pyruvate dampens postbypass myocardial inflammation. METHODS Pigs were maintained on cardiopulmonary bypass while their hearts were arrested for 60 minutes with 4:1 blood:crystalloid cardioplegia, in which the crystalloid contained 188 mM glucose ± 24 mM pyruvate. Pigs were weaned from bypass after 30 minutes of whole blood reperfusion and recovered for 4 hours. Glutathione (GSH) and glutathione disulfide (GSSG) were measured in coronary sinus plasma to indirectly monitor myocardial GSH redox state (GSH/GSSG). Left ventricular myocardium was sampled 4 hours after cardiopulmonary bypass for analyses of C-reactive protein, matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinase-2 (TIMP-2), and to assess neutrophil infiltration by histology and myeloperoxidase assay. RESULTS Coronary sinus GSH/GSSG fell 70% after cardiopulmonary bypass with control cardioplegia, but pyruvate cardioplegia produced a robust increase in coronary sinus GSH/GSSG that persisted for 4 hours after bypass. Myocardial C-reactive protein content increased 5.6-fold after control bypass, and neutrophil infiltration and myeloperoxidase activity also increased, but pyruvate-fortified cardioplegia prevented these inflammatory effects. Control cardioplegia lowered myocardial TIMP-2 content by 59% and increased matrix metalloproteinase-9 activity by 35% versus nonbypass sham values, but pyruvate cardioplegia increased TIMP-2 content ninefold versus control cardioplegia and prevented the increase in matrix metalloproteinase-9. Matrix metalloproteinase-2 was not affected by bypass ± pyruvate. CONCLUSIONS Pyruvate-enriched cardioplegia dampens cardiopulmonary bypass-induced myocardial inflammation. Increased GSH/GSSG and TIMP-2 may mediate pyruvates effects.

Peri- and intra-operative management of the goat during acute surgical experimentation

Goats are used as animal models for surgery and trauma research. The authors discuss appropriate methods for induction of anesthetics, intubation and surgical maintenance of the goat during acute experimentation. Risks imposed by the Q fever pathogen Coxiella burnetii are described, as well as measures that have proven effective in minimizing zoonotic transmission of this pathogen to laboratory personnel. With appropriate knowledge of its applications, peri- and intra-operative management and limitations, the goat is a suitable animal model for a variety of biomedical research applications.

Field-Improvised War Surgery in Kosovo: Use of Kitchen Utensils as Surgical Instruments

After years of conflict between Serbia and neighboring Kosovo, a full-blown war started in March 1999 when the Serbian and Yugoslav armies began a statewide military crackdown against ethnic Albanians and the Kosovo Liberation Army. Most ethnic Albanians were displaced to Macedonia or Albania. Some, however, found refuge in the Molopolce mountain region of Kosovo among military personnel, thus necessitating the creation of a field medical facility. Patient treatment at the field-improvised Nerodime Military Hospital, and the management of work took place under very difficult conditions including a chronic lack of appropriate medical equipment. Improvised lifesaving surgeries were performed with kitchen utensils serving as retractors at the field hospital. This article compares the treatment of patients between the two hospitals, and is the first article to date describing the war experience in general at the field hospitals in Kosovo.

Reactive oxygen species mediate robust cardioprotection induced by intermittent hypoxia conditioning

preconditioning protocol, and group 4 was preconditioned with low concentration (3 uM) of ONOO−. Isolated hearts were then subjected to 30 min test ischemia followed by 120 reperfusion. At the end of reperfusion infarct size were measured using triphenyl-tetrazolium staining. Ischemic preconditioning and ONOO− administration significantly reduced infarct size and lactate dehydrogenase (LDH) release when compared to control (5.7±2.0 and 13.1±4.1% vs. 45.0±3.8% and 0.12±0.041 and 0.11±0.03 mU min g vs. 0.31±0.06). FeTPPS administration prevents the beneficial effect of preconditioning (infarct size: 37.6± 6.9%, LDH release 30.7±0.05 mU min g). We conclude that peroxynitrite at low concentrations is necessary to the infarct size limiting effect of preconditioning in rat hearts.