Robert T. Mallet

Intermittent hypoxic training protects canine myocardium from Infarction

This investigation examined cardiac protective effects of normobaric intermittent hypoxia training. Six dogs underwent intermittent hypoxic training for 20 consecutive days in a normobaric chamber ventilated intermittently with N2 to reduce fraction of inspired oxygen (Fio2) to 9.5%–10%. Hypoxic periods, initially 5 mins and increasing to 10 mins, were followed by 4-min normoxic periods. This hypoxia-normoxia protocol was repeated, initially 5 times and increasing to 8 times. The dogs showed no discomfort during intermittent hypoxic training. After 20 days of hypoxic training, the resistance of ventricular myocardium to infarction was assessed in an acute experiment. The left anterior descending (LAD) coronary artery was occluded for 60 mins and then reperfused for 5 hrs. At 30 mins of LAD occlusion, radioactive microspheres were injected through a left atrial catheter to assess coronary collateral blood flow into the ischemic region. After 5 hrs reperfusion, the heart was dyed to delineate the area at risk (AAR) of infarction and stained with triphenyl tetrazolium chloride to identify infarcted myocardium. During LAD occlusion and reperfusion, systemic hemodynamics and global left ventricular function were stable. Infarction was not detected in 4 hearts and was 1.6% of AAR in the other 2 hearts. In contrast, 6 dogs sham-trained in a chamber ventilated with compressed air and 5 untrained dogs subjected to the same LAD occlusion/reperfusion protocol had infarcts of 36.8% ± 5.8% and 35.2% ± 9.5% of the AAR, respectively. The reduction in infarct size of four of the six hypoxia-trained dogs could not be explained by enhanced collateral blood flow to the AAR. Hypoxia-trained dogs had no ventricular tachycardia or ventricular fibrillation. Three sham-trained dogs had ventricular tachycardia and two had ventricular fibrillation. Three untrained dogs had ventricular fibrillation. In conclusion, intermittent hypoxic training protects canine myocardium from infarction and life-threatening arrhythmias during coronary artery occlusion and reperfusion. The mechanism responsible for this potent cardioprotection merits further study.

Insulin improves contractile function during moderate ischemia in canine left ventricle

This study determined the effects of insulin on myocardial contractile function and glucose metabolism during moderate coronary hypoperfusion. Coronary perfusion pressure (CPP) was lowered from 100 to 60, 50, and 40 mmHg in the left anterior descending coronary artery of anesthetized, open-chest dogs. Regional glucose uptake (GU), lactate uptake, myocardial O2 consumption, and percent segment shortening (%SS) were measured without (n = 12) or with intravenous (4 U/min, n = 12) or intracoronary insulin (4 U/min, n = 6). Glucose metabolites were also measured in freeze-clamped biopsies of control heart (n = 6) and hearts treated with intravenous insulin (n = 6) at the completion of the protocol (40 mmHg CPP). GU increased with intravenous and intracoronary insulin (P < 0.01). In all groups, GU was unaffected by reduced CPP, although lactate uptake decreased significantly (P < 0.01). Myocardial O2 consumption fell (P < 0.05) as CPP was lowered in all groups and was not altered significantly by intravenous or intracoronary insulin treatment. Without insulin, %SS decreased 72% (P < 0.05) at 40 mmHg CPP, but in hearts treated with intravenous and intracoronary insulin, %SS was not reduced (P > 0.05). Myocardial glycogen, alanine, lactate, and pyruvate contents were not significantly different in untreated hearts and hearts treated with intravenous insulin. Thus, in moderately ischemic canine myocardium, insulin markedly improved regional contractile function and did not appreciably increase the products of anaerobic glucose metabolism.This study determined the effects of insulin on myocardial contractile function and glucose metabolism during moderate coronary hypoperfusion. Coronary perfusion pressure (CPP) was lowered from 100 to 60, 50, and 40 mmHg in the left anterior descending coronary artery of anesthetized, open-chest dogs. Regional glucose uptake (GU), lactate uptake, myocardial O2 consumption, and percent segment shortening (%SS) were measured without ( n = 12) or with intravenous (4 U/min, n = 12) or intracoronary insulin (4 U/min, n = 6). Glucose metabolites were also measured in freeze-clamped biopsies of control heart ( n = 6) and hearts treated with intravenous insulin ( n = 6) at the completion of the protocol (40 mmHg CPP). GU increased with intravenous and intracoronary insulin ( P < 0.01). In all groups, GU was unaffected by reduced CPP, although lactate uptake decreased significantly ( P < 0.01). Myocardial O2 consumption fell ( P < 0.05) as CPP was lowered in all groups and was not altered significantly by intravenous or intracoronary insulin treatment. Without insulin, %SS decreased 72% ( P < 0.05) at 40 mmHg CPP, but in hearts treated with intravenous and intracoronary insulin, %SS was not reduced ( P > 0.05). Myocardial glycogen, alanine, lactate, and pyruvate contents were not significantly different in untreated hearts and hearts treated with intravenous insulin. Thus, in moderately ischemic canine myocardium, insulin markedly improved regional contractile function and did not appreciably increase the products of anaerobic glucose metabolism.

Novel Split Chest Tube Improves Post-Surgical Thoracic Drainage

Objective Conventional, separate mediastinal and pleural tubes are often inefficient at draining thoracic effusions. Description We developed a Y-shaped chest tube with split ends that divide within the thoracic cavity, permitting separate intrathoracic placement and requiring a single exit port. In this study, thoracic drainage by the split drain vs. that of separate drains was tested. Methods After sternotomy, pericardiotomy, and left pleurotomy, pigs were fitted with separate chest drains (n=10) or a split tube prototype (n=9) with internal openings positioned in the mediastinum and in the costo-diaphragmatic recess. Separate series of experiments were conducted to test drainage of D5W or 0.58 M sucrose, an aqueous solution with viscosity approximating that of plasma. One litre of fluid was infused into the thorax, and suction was applied at −20 cm H2O for 30 min. Results When D5W was infused, the split drain left a residual volume of 53 ± 99 ml (mean value ± SD) vs. 148 ± 120 for the separate drain (P=0.007), representing a drainage efficiency (i.e. drained vol/[drained + residual vol]) of 95 ± 10% vs. 86 ± 12% for the separate drains (P = 0.011). In the second series, the split drain evacuated more 0.58 M sucrose in the first minute (967 ± 129 ml) than the separate drains (680 ± 192 ml, P<0.001). By 30 min, the split drain evacuated a similar volume of sucrose vs. the conventional drain (1089 ± 72 vs. 1056 ± 78 ml; P = 0.5). Residual volume tended to be lower (25 ± 10 vs. 62 ± 72 ml; P = 0.128) and drainage efficiency tended to be higher (98 ± 1 vs. 95 ± 6%; P = 0.111) with the split drain vs. conventional separate drains. Conclusion The split chest tube drained the thoracic cavity at least as effectively as conventional separate tubes. This new device could potentially alleviate postoperative complications.

Hold that thought: Induction of erythropoietin to protect the ischemic brain

Methods: Isolated hearts from wild type (WT: C57BL/6NCrL), ERα-/-, ERβ-/and GPER1-/were perfused using Langendorff apparatus with Krebs Henseleit buffer (control) or with the addition of estrogen (40 nM). Hearts were subjected to 18 min global ischemia followed by 60 min reperfusion. Cardiac function was recorded during the entire experiment and myocardial infarct size was measured by TTC staining at the end of the reperfusion. Mitochondria calcium retention capacity (CRC) required to induce the mitochondrial permeability transition pore (mPTP) opening were assessed after 10 min reperfusion. Protein levels were measured by Western Blot in whole heart lysates after 5 min treatment just before ischemia, and after 10 min reperfusion. LY294002 and U0126 were used as inhibitor of PI-3K/Akt, and MAPK/ERK translocation, respectively.Methods: Sprague Dawley rats and C57BL6 mice (wt and MnSODtg) were infected with T. cruzi. Infected rats were treated with phenyl-alpha-tert-butylnitrone (PBN-antioxidant) and/or benzonidazole (BZ-anti-parasite). We monitored myocardial parasite burden, oxidative adducts, mitochondrial complex activities, respiration and ATP synthesis rates, and inflammatory and cardiac remodeling responses during disease development. Cardiac hemodynamics was determined for all rats.D the war in Croatia, from 1991-1995, the majority of patients with CAD were treated conservatively. Revascularization was performed only rarely for ACS patients. In the “Ere of stentomania, 1995-2005”, which due to the limited resources “flamed” in Croatia in smaller intensity than possibly elsewhere, and before the COURAGE-Ere, I performed over 8000 diagnostical procedures and over 1200 PCI-procedures.Methods: An ECLS transport team implanted an ECMO at the site of the primary care center with subsequent transport of the patient to the tertiary care center. Between September 2009 and November 2013, 14 patients with ARDS or cardiogenic chock were treated by our ECLS transport team. Mean age was 43.7±13.6 years. All implantations were done percutaneously.11 patients received an ECMO in veno-venous configuration, two patients in veno-arterial and one patient in veno-venoarterial configuration.: The heart is believed to escape serious direct injury during the administration of closed chest cardiopulmonary resuscitation (CPR). However, no comprehensive histologic studies of the coronary arteries or the atrioventricular conduction system have been performed to determine whether these structures might be injured by CPR. This report includes a retrospective review of 105 human hearts extensively studied at autopsy after the injection of a colored barium gelatin mass into the coronary arteries. The study group, 83 males and 22 females, included 63 patients (60%) who died in the hospital. Eighty patients (76%) received CPR immediately prior to death. Evidence consistent with direct blunt injury to the coronary arteries and/or the His Bundle was found in 35 (44%) patients who received CPR. These structural changes were characterized by fracture and disruption of the coronary artery wall and/or hemorrhage into the region of the branching His Bundle. Females were significantly older and showed a significantly higher frequency of these lesions than males. Injuries were not related to the site where CPR was administered, in- or out-of-hospital, nor to the duration of CPR. We conclude that CPR is associated with evidence of direct blunt injury to the coronary arteries and/or the His Bundle and proximal bundle branches; and that these lesions may influence the outcome of resuscitative efforts as well as ultimate prognosis.The heart is believed to escape serious direct injury during the administration of closed chest cardiopulmonary resuscitation (CPR). However, no comprehensive histologic studies of the coronary arteries or the atrioventricular conduction system have been performed to determine whether these structures might be injured by CPR. This report includes a retrospective review of 105 human hearts extensively studied at autopsy after the injection of a colored barium gelatin mass into the coronary arteries. The study group, 83 males and 22 females, included 63 patients (60%) who died in the hospital. Eighty patients (76%) received CPR immediately prior to death. Evidence consistent with direct blunt injury to the coronary arteries and/or the His Bundle was found in 35 (44%) patients who received CPR. These structural changes were characterized by fracture and disruption of the coronary artery wall and/or hemorrhage into the region of the branching His Bundle. Females were significantly older and showed a significantly higher frequency of these lesions than males. Injuries were not related to the site where CPR was administered, in- or out-of-hospital, nor to the duration of CPR. We conclude that CPR is associated with evidence of direct blunt injury to the coronary arteries and/or the His Bundle and proximal bundle branches; and that these lesions may influence the outcome of resuscitative efforts as well as ultimate prognosis.R hypertension (RH) has been a nightmare for both specialists and primary care physicians. RH comprises up to 2025% of patients who are enrolled in hypertension related trials. The risk of cardiovascular events is significantly increased in patients with resistant hypertension. The management of this condition also utilizes excessive health care resources. Several complex neural and humeral physiological processes coordinate the regulation of blood pressure. The autonomic nervous system plays a very important role especially through its sympathetic component. The peri-renal arterial sympathetic fibers and those at the region of carotid sinus are important in blood pressure modulation.OBJECTIVEnTo investigate localization and distribution of integrin subunit β1, β2 and β3 and morphological changes of ligand-recepter binding in thrombi of acute pulmonary embolism (PE) patients and explore activation of circulated immune cells, inflammatory immune adherence and coagulation response in acute venous thrombosis.nnnMETHODSnThrombi were collected from patients with acute PE. Immunohistochemistry was done to detect the expression and distribution of integrin β1, β2 and β3 in cells within thrombi, and ligands of integrin subunit β1, β2 and β3 were also determined by immunohistochemistry within the thrombi.nnnRESULTSn1) Acute venous thrombi were red thrombi composed of skeletons and filamentous mesh containing large amounts of red blood cells and white blood cells; 2) Integrin subunit β1, β2 and β3 were expressed on lymphocytes, neutrophils and platelets; 3) No expression of integrin β1 ligands: Laminin, Fibronectin, Collagen I or Collagen-II on lymphocytes; integrin β2 ligands including ICAM, factor X and iC3b are distributed on neutrophils, and ligand fibrinogen bound to neutrophils; integrin β3 was expressed on platelets which form the skeleton of thrombi and bound to fibrinogen to construct mesh structure; 4) Factor Xa was expressed on the filamentous mesh; 5) Filamentous mesh was fully filled with red blood cell dominant blood cells.nnnCONCLUSIONnAcute venous thrombosis is an activation process of circulated lymphocytes, neutrophils and platelets mainly, and a whole process including integrin subunit β2 and β3 binding with their ligands. Activation of immune cells, inflammatory immune adherence and coagulation response are involved in the acute venous thrombosis.