Mahmoud Loubani

Autotransplantation of unmanipulated bone marrow into scarred myocardium is safe and enhances cardiac function in humans.

Stem cell transplants into damaged myocardium may have the potential to improve cardiac function. We investigated the safety of transplanting unmanipulated autologous bone marrow into infarcted myocardium of patients undergoing coronary bypass surgery and assessed its efficacy to improve cardiac function. Fourteen patients with one or more areas of transmural myocardial infarction were studied. Autologous bone marrow was obtained by sternal bone aspirate at the time of surgery, diluted in autologous serum at a ratio of 1:2, and then injected 1 cm apart into the mid-depth of the left ventricular scar. There were no deaths, no perioperative myocardial infarctions, and no significant ventricular arrhythmias. Dobutamine stress echocardiography demonstrated overall improvement in the global and regional left ventricular function 6 weeks and 10 months after surgery. Of 34 infarcted left ventricular segments, 11 were injected with bone marrow alone, 13 were revascularized with a bypass graft alone, and 10 received bone marrow transplantation and a bypass graft in combination. Only the left ventricle segmental wall motion score of the areas injected with bone marrow and receiving a bypass graft in combination improved at low dose and at peak dobutamine stress. These findings suggest that transplantation of unmanipulated autologous bone marrow into scar tissue of the human heart is safe and enhances cardiac function only when used in combination with myocardial revascularization. This benefit can be seen after 6 weeks of the bone marrow transplant and is maintained after 10 months of follow-up.

Pharmacological and ischemic preconditioning of the human myocardium: mitoK ATP channels are upstream and p38MAPK is downstream of PKC

BackgroundThese studies investigate the role of mitoKATP channels, protein kinase C (PKC) and Mitogen activated protein kinase (p38MAPK) on the cardioprotection of ischemic (IP) and pharmacological preconditioning (PP) of the human myocardium and their sequence of activation.ResultsRight atrial appendages from patients undergoing elective cardiac surgery were equilibrated for 30 min and then subjected to 90 min of simulated ischemia followed by 120 min reoxygenation. At the end of each protocol creatinine kinase leakage (CK U/g wet wt) and the reduction of MTT to formazan dye (mM/g wet wt) were measured. Similar protection was obtained with α1 agonist phenylephrine, adenosine and IP and their combination did not afford additional cardioprotection. Blockade of mitoKATP channels with 5-hydroxydecanoate, PKC with chelerythrine, or p38MAPK with SB203580 abolished the protection of IP and of PP. In additional studies, the stimulation of mitoKATP channels with diazoxide or activation of PKC with PMA or p38MAPK with anisomycin induced identical protection to that of IP and PP. The protection induced by diazoxide was abolished by blockade of PKC and by blockade of p38MAPK. Furthermore, the protection induced by PMA was abolished by SB203580 but not by 5-hydroxydecanoate, whereas the protection induced by anisomycin was unaffected by either 5-hydroxydecanoate or chelerythrine.ConclusionsOpening of mitoKATP channels and activation of PKC and p38MAPK are obligatory steps in the signal transduction cascade of IP and PP of the human myocardium with PKC activation being downstream of the opening of mitoKATP channels and upstream of p38MAPK activation.

The aging human myocardium: tolerance to ischemia and responsiveness to ischemic preconditioning

BACKGROUNDnIncreasing age has been recognized as a cause for adverse prognosis in the setting of myocardial infarction, coronary angioplasty, and cardiac surgery. This is attributed to a greater susceptibility of the senescent heart to ischemic injury and to a lower response to protective interventions. This study investigated the effect of aging on the tolerance to ischemia of the human myocardium and its response to ischemic preconditioning.nnnMETHODSnRight atrial specimens from 128 patients undergoing elective heart surgery were collected, sliced, and equilibrated for 30 minutes before being randomized into 3 study protocols: (1) 210 minutes of aerobic incubation (time-matched control), (2) 90 minutes of simulated ischemia and 120 minutes of reoxygenation, and (3) ischemic preconditioning with 5 minutes of ischemia and 5 minutes of reoxygenation before 90 minutes of ischemia and 120 minutes of reoxygenation. Patients were subdivided into 3 age groups: 30 to 49 years, 50 to 69 years, and 70 to 90 years. At the end of each protocol, tissue injury and viability were assessed by the leakage of creatine kinase and the reduction of 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide to insoluble formazan dye.nnnRESULTSnThere were no differences among the 3 groups of patients in their comorbid conditions or their cardiac medications. Ischemic injury was similar in all 3 groups (creatine kinase = 4.1 +/- 0.7, 3.6 +/- 1.0, and 4.3 +/- 1.1 U/g wet weight, respectively; 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide = 64.7 +/- 31.3, 96.3 +/- 32.0, and 61.0 +/- 30.4 mM/g wet weight, respectively, P = not significant in all cases), and ischemic preconditioning equally protected against ischemia at all ages (creatine kinase = 1.9 +/- 0.5, 1.8 +/- 0.4, and 2.1 +/- 0.6 U/g wet weight, respectively; 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide = 157.9 +/- 31.5, 170.7 +/- 35.3, and 138.4 +/- 43.8 mM/g wet weight, respectively; P <.05 in all cases vs ischemia alone).nnnCONCLUSIONnAge does not influence the tolerance of the human myocardium to ischemia or the protective effect of ischemic preconditioning. These results indicate the need for a reevaluation of the importance of age in risk scoring in cardiac surgery.

Residual atrial fibrillation and clinical consequences following postoperative supraventricular arrhythmias

AIMSnThis retrospective study investigated whether the supraventricular arrhythmias (SVA) observed during cardiac surgery are limited to or persist beyond the postoperative period, their clinical consequences and whether they are influenced by preoperative and postoperative factors.nnnMETHODSnA total of 375 patients undergoing elective bypass graft surgery over a 15-month period by three surgeons were included. All patients had their preoperative medications continued to the day of surgery and prophylactic anti-arrhythmic medications were not used in any of the cases. Standard anaesthetic techniques were used. Rhythm disturbances were diagnosed by ECG. The arrhythmias were treated medically or by cardioversion. All patients were followed up for 6 months.nnnRESULTSnPostoperative SVA occurred in 25% of patients. The commonest arrhythmia was atrial fibrillation (89.4%), followed by atrial flutter (6.4%) and supraventricular tachycardia (4.2%). In 89. 8% of the cases, the arrhythmias occurred within the first four postoperative days with a maximum incidence on the second day (27. 7%). Atrial fibrillation was still present in 50% of patients at hospital discharge and in 39% at 6 months follow up. Patients with arrhythmias had a prolonged hospital stay (7.7+/-2.6 vs. 6.0+/-2.6 days; P<0.05). There was no hospital mortality in the study and the incidence of postoperative stroke was equal in the sinus rhythm and arrhythmia patients (1.1%). SVA were more frequent when cardioplegia was used to protect the heart (32%) than with intermittent ischaemia (9%; P<0.001). At 6 months follow up, the patients receiving cardioplegia also had a higher prevalence of atrial fibrillation than those operated with intermittent ischaemia (41% vs. 22%; P<0. 05). The incidence of SVA and persistence of atrial fibrillation was unrelated to other preoperative and intraoperative factors.nnnCONCLUSIONnPostoperative supraventricular arrhythmias have a long-lasting effect on cardiac rhythm: patients with SVA have a high probability of remaining in atrial fibrillation at hospital discharge and 6 months after surgery. The occurrence of atrial fibrillation seems to be influenced by the type of myocardial protection used but this does not appear to exert harmful effects.

Does the type of prosthesis influence early left ventricular mass regression after aortic valve replacement? Assessment with magneticresonance imaging

BACKGROUNDnDebate exists regarding selection of the prosthesis type most likely to maximize early left ventricular (LV) mass regression after aortic valve replacement (AVR) for stenotic valvular disease. The aim of this study was to compare the degree of LV mass regression measured by MRI 6 months after prospectively randomized valve implantation for two biological prostheses, stented and stentless, and for two mechanical valves, tilting disc and bileaflet.nnnMETHODSnThirty-nine consecutive patients with predominant aortic stenosis accepted for elective AVR were studied. Twenty patients requiring a tissue prosthesis were randomly assigned to receive either a Freestyle or Mosaic valve. The remaining 19 patients in whom mechanical prosthesis was indicated were randomly assigned to receive either an Ultracor or an ATS valve.nnnRESULTSnThere was no difference in valve size implanted between the compared groups. LV mass measurements were performed with MRI (1.5-T Vision, Siemens, Germany) immediately before and 6 months after surgery. All valve types produced significant postoperative reduction in LV mass compared with preoperative values (P <.01). Percent change in LV mass regression was similar between the two porcine valve types, Mosaic (24.4% +/- 11.1%) and Freestyle (21.1% +/- 16.7%), and between the two mechanical valve designs, Ultracor (19.3% +/- 9.5%) and ATS (26.3% +/- 10.8%), respectively.nnnCONCLUSIONSnSignificant LV remodeling occurs early after AVR for aortic stenosis. The degree of regression in LV mass is independent of prosthesis type implanted.

Early discharge following coronary bypass surgery: is it safe?

OBJECTIVESnEarly discharge has been proposed as a means of containing the escalating cost of health care in cardiac surgery. The aim of this study was to investigate whether shortening the length of hospital stay after coronary artery bypass surgery is safe and cost effective.nnnMETHODSnPatients (n=198) undergoing elective bypass surgery by two surgeons for a period of 12 months were prospectively entered into the study but not randomized. The anaesthetic and surgical treatments were identical in all patients with the exception that one of the surgeons used intermittent cold crystalloid cardioplegia (normal discharge group; n=119) and the other used intermittent ischaemia without cardioplegia (early discharge group; n=79). Previous to the study both surgeons discharged patients on the 7th-8th postoperative day. For the present study, one of the two surgeons adopted the new policy of discharging patients on the 4th postoperative day (early discharge group). The criteria for hospital discharge included: presence of sinus rhythm, absence of pyrexia and wound infection, normal routine blood tests, satisfactory chest X-ray and ECG and full mobility.nnnRESULTSnThe clinical characteristics were identical in the two groups. The number of grafts per patient was 2.8+/-0.8 and 3.2+/-1.0, and the total ischaemic time 47+/-13 and 46+/-14 min in the normal and early discharge groups, respectively (P=NS in each instance). In the normal discharge group the mean hospital stay was 7.7+/-3.3 days whereas in the early discharge group it was 4.7+/-2.0 days (P<0. 0001) with 73.5% of the patients being discharged within the first 4 days following surgery. The shortening of hospital stay resulted in a mean reduction of costs of pound750/patient. There was no operative mortality (<30 days following surgery) and the incidence of non-fatal perioperative complications were similar in the two groups, with the exception that the incidence of supraventricular arrhythmias was significantly higher in the normal discharge group than in the early discharge group (33% vs. 6.3% respectively; P<0. 0001). These rhythm abnormalities occurred within the first 4 days in 89% of patients following surgery and were the cause of readmission in only one patient in the normal discharge group. There were a total of ten (8.4%) readmissions in the normal discharge group and three (3.8%) in the early discharge group.nnnCONCLUSIONnShortening the postoperative hospital stay to 4 days following elective coronary bypass surgery appears to be safe and can be a means of reducing the cost of care. This in turn may result in a greater availability of resources and in an effective way of reducing waiting lists.

Mid-term results of combined transmyocardial laser revascularization and coronary artery bypass

BACKGROUNDnTransmyocardial laser revascularization is increasingly used to treat intractable angina in the absence of graftable vessels; however, its role in combination with coronary artery bypass grafting remains undefined. The aim of this pilot study was to investigate the outcome of the combination therapy at mid-term follow-up.nnnMETHODSnPatients (n = 20) who had elective coronary artery bypass with one or more nongraftable coronary arteries were prospectively randomized to have either coronary artery bypass grafting alone or combination coronary artery bypass grafting plus transmyocardial laser revascularization with a holmium:YAG (yttrium-aluminum-garnet) laser to nongraftable areas. All patients had an exercise tolerance test preoperatively and at 6, 18, and 36 months follow-up. Stress echocardiography was performed on 17 patients at 18 months postoperatively, and regional wall motion score index was calculated in lased and nonlased nonrevascularizable myocardium of the left ventricle at rest and with dobutamine stress.nnnRESULTSnBoth groups of patients were similar in preoperative demographics and operative data. There was no perioperative death. There was no difference between the two groups in angina scoring at 6, 18, and 36 months follow-up. Exercise tolerance improved by a mean of 46.8 +/- 20.0 seconds in the coronary artery bypass grafting group versus 199.2 +/- 66.5 seconds per patient in the coronary artery bypass grafting plus transmyocardial laser revascularization group (p = 1.8 x10(-6)) at 6 months; this benefit was maintained at 18 months (157 +/- 46.3 versus 61 +/- 39.2 seconds; p = 4 x10(-4)) but was lost at 36 months (57.2. +/- 42.1 versus 68.1 +/- 46.7 seconds; p = 0.70). The mean values for wall motion score index in the lased and nonlased regions at each stage of dobutamine stress at 18 months after surgery were not statistically significant.nnnCONCLUSIONSnThe combination of coronary artery bypass and transmyocardial laser revascularization improved exercise tolerance in patients in whom complete revascularization could not be achieved by bypass grafting alone in the short term, but this benefit was lost by 36 months postoperatively. The transient improvement in exercise tolerance cannot be explained by changes in contractility in the lased areas.

Validation of the Intensive Care National Audit and Research Centre Scoring System in a UK Adult Cardiac Surgery Population

OBJECTIVEnThe Intensive Care National Audit and Research Centre (ICNARC) scoring system was conceived in 2007, utilizing 12 physiologic variables taken from the first 24 hours of adult admissions to the general intensive care unit (ICU) to predict in-hospital mortality. The authors aimed to evaluate the ICNARC score in predicting mortality in cardiac surgical patients compared to established cardiac risk models such as logistic EuroSCORE as well as to the Acute Physiology and Chronic Health Evaluation (APACHE) II.nnnDESIGNnRetrospective analysis of data collected prospectively.nnnSETTINGnSingle-center study in a cardiac intensive care in a regional cardiothoracic center.nnnPARTICIPANTSnPatients undergoing cardiac surgery between January 2010 and June 2012.nnnMETHODSnA total of 1,646 patients were scored preoperatively using the logistic EuroSCORE and postoperatively using ICNARC and APACHE II. Data for comparison of scoring systems are presented as area under the receiver operating characteristic curve.nnnMEASUREMENTS AND MAIN RESULTSnThe mean age at surgery was 67 years±10.1. The mortality from all cardiac surgery was 3.2%. The mean logistic EuroSCORE was 7.31±10.13, the mean ICNARC score was 13.42±5.055, while the mean APACHE II score was 6.32±7.731. The c-indices for logistic EuroSCORE, ICNARC, and APACHE II were 0.801, 0.847 and 0.648, respectively.nnnCONCLUSIONnThe authors have, for the first time, validated the ICNARC score as a useful predictor of postoperative mortality in adult cardiac surgical patients. This could have implications for postoperative management, focusing the utilization of resources as well as a method to measure and compare performance in the cardiothoracic ICU.

Characterization of optimal resting tension in human pulmonary arteries

AIM To determine the optimum resting tension (ORT) for in vitro human pulmonary artery (PA) ring preparations. METHODS Pulmonary arteries were dissected from disease free sections of the resected lung in the operating theatre and tissue samples were directly sent to the laboratory in Krebs-Henseleit solution (Krebs). The pulmonary arteries were then cut into 2 mm long rings. PA rings were mounted in 25 mL organ baths or 8 mL myograph chambers containing Krebs compound (37 °C, bubbled with 21% O2: 5% CO2) to measure changes in isometric tension. The resting tension was set at 1-gram force (gf) with vessels being left static to equilibrate for duration of one hour. Baseline contractile reactions to 40 mmol/L KCl were obtained from a resting tension of 1 gf. Contractile reactions to 40 mmol/L KCl were then obtained from stepwise increases in resting tension (1.2, 1.4, 1.6, 1.8 and 2.0 gf). RESULTS Twenty PA rings of internal diameter between 2-4 mm were prepared from 4 patients. In human PA rings incrementing the tension during rest stance by 0.6 gf, up to 1.6 gf significantly augmented the 40 mmol/L KCl stimulated tension. Further enhancement of active tension by 0.4 gf, up to 2.0 gf mitigate the 40 mmol/L KCl stimulated reaction. Both Myograph and the organ bath demonstrated identical conclusions, supporting that the radial optimal resting tension for human PA ring was 1.61 g. CONCLUSION The radial optimal resting tension in our experiment is 1.61 gf (15.78 mN) for human PA rings.

Coronary Artery Bypass Surgery for Patients Presenting with Ventricular Arrhythmias: Propensity Matched Early and Late Outcome

Objectives: Patients with ischemic ventricular arrhythmia (IVA) in the form of nfibrillation or tachycardia represent a surgical challenge. Evidence in the nliterature suggests that ventricular arrhythmia threatens survival even after ncardiac surgery. We aim to review the results of our patients presenting with nIVA with regard to short and long term outcome following cardiac surgery. nMethods: This was a retrospective study of data entered prospectively into our ncardiac surgical database between January 1999 and September 2015. A total of n9609 patients underwent Cardiac Surgery which included 54 patients after nsurviving IVA. The short- and long-term outcomes were compared to a propensity matched group. nActuarial survival was calculated using Kaplan Meier analysis. Results: The 54 study group patients were propensity matched on a 1:2 basis with na control group of non-IVA (n = 108). The baseline preoperative ncharacteristics and risk factors were similar between the 2 groups and all ncases underwent CABG only. Univariate analysis showed pacing postoperatively n(33.3 vs 66.7%; p = 0.001) and postoperative ventricular arrhythmia (10 vs 22.2%; p = 0.039) to be significantly higher in the IVA group. Cox-multivariate nanalysis showed postoperative ventricular arrhythmia in either group (Hazard nratio = 1.5) to be the only significant factor to impact mortality (p 0.001). Long term survival was not significantly different between the ntwo groups (10.4; CI: 9.08 - 11.75 vs 9.3; CI: 7.61 - 11.01 yrs, p = 0.3). Conclusion: Cardiac surgery on patients presenting with IVA can be performed safely nyielding short and long term results equivalent to non-IVA cases. These patients should not be denied surgery with consideration nof good long term outcome.