Biomedical subjects

Yousuf Mahomed

Publications and source records attributed to Yousuf Mahomed.

6 recordsLinked to original sources

PubMed2006

Fate of the autograft and homograft following Ross aortic valve replacement: reoperative frequency, outcome, and management.

BACKGROUND AND AIM OF THE STUDY: The optimal hemodynamic performance and potential for growth of the pulmonary autograft has led to expanded indications for the Ross aortic valve replacement (AVR) procedure in some centers. The authors' institutional mid-term experience was reviewed to assess autograft and homograft hemodynamics, growth profile of the autograft, and reoperative frequency following Ross AVR. METHODS: Between June 1993 and June 2005, 167 consecutive patients (mean age 24.9 +/- 15.5 years; range: 1 month to 61 years) underwent Ross AVR: 48% of patients were aged < 19 years. Additional procedures (n = 78) were performed in 55 patients (33%) at the time of the Ross procedure. In total, 151 patients had isolated aortic valve disease and 16 pediatric patients had more complex, multi-level left ventricular outflow tract obstruction. RESULTS: There were two early deaths (1.2%) and one late death (0.6%) over a mean follow up of 5.1 +/- 3.0 years (range: 1 month to 11 years). Actuarial survival at 10 years was 98%. In pediatric patients with Konno procedure (n = 16), the pulmonary autograft mean annulus diameter increased from 10.2 to 19.9 mm. Twelve patients underwent 12 reoperations without mortality for autograft insufficiency or an ascending aortic aneurysm at a median interval of 5 years (range: 2 to 8 years): aortic annuloplasty and ascending aorta replacement (n = 4), composite aortic root replacement (n = 7), and repair of left ventricular pseudoaneurysm (n = 1). Freedom from replacement of the pulmonary autograft was 96% at 10 years. Five of the 164 surviving patients (3%) developed significant obstruction of the pulmonary homograft and required conduit replacement at a median of four years. CONCLUSION: The Ross AVR can be performed with good mid-term results, including the pediatric age group. The potential for development of significant autograft insufficiency and homograft stenosis warrants annual follow up through the intermediate and late terms.

Adolescent↗

PubMed2005

Does endogenous testosterone mediate the lower preconditioning threshold in males?

BACKGROUND: Preconditioning is injury-induced protection from subsequent insult. Recent data indicates that males have lower preconditioning thresholds compared to females. Therefore, we hypothesized that testosterone may mediate the lower preconditioning threshold observed in males. MATERIALS AND METHODS: Adult normal and castrated male Sprague-Dawley rats (n = 4-5) were given intraperitoneal (i.p.) injections of 125 or 500 microg/kg Salmonella typhimurium lipopolysaccharide (ETX) or 0.4 ml normal saline (NS). Another i.p. injection of 500 microg/kg ETX (injury dose) was given 24 h later. After 6 h, myocardial function was evaluated via the Langendorff perfusion model. Shams received only NS, while non-preconditioned rats (PC-) received NS followed by the 500 microg/kg ETX injury dose. Preconditioned rats received injections of 125 mug/kg ETX (PC +125) or 500 microg/kg ETX (PC +500), followed by the 500 microg/kg ETX injury dose. RESULTS: Normal PC +125 and PC +500 males were preconditioned and maintained cardiac function similar to shams (P > 0.05). Castrated PC +125 and PC +500 males were also preconditioned and maintained cardiac function similar to castrated shams (P > 0.05). Conversely, both normal and castrated PC-males showed significantly decreased cardiac function compared to shams (P < 0.05). CONCLUSIONS: Endogenous testosterone does not mediate the lower preconditioning threshold in males.

Animals↗

PubMed2005

p38 mitogen activated protein kinase mediates both death signaling and functional depression in the heart.

BACKGROUND: Understanding the myocardial inflammatory response to ischemia is an important part of achieving the elusive clinical goal of long-enduring myocardial protection. p38 mitogen-activated protein kinase (MAPK) has been implicated in oxidant stress-induced myocardial tumor necrosis factor production. However, it is unknown whether p38 MAPK mediates the following important events in both myocardial apoptosis and functional depression: mitogen-activated protein kinase-activated protein kinase 2, caspase-1, caspase-3, and caspase-11 activation, and tumor necrosis factor, interleukin-1beta and interleukin-6 production. METHODS: Isolated rat hearts were perfused and subjected to an ischemia-reperfusion insult, with and without preischemic infusion of 20 microM SB203580 (p38 MAPK inhibitor). Myocardial functional measurements were continuously recorded throughout the experiments. Myocardial tissue was then assessed for products of p38 MAPK activation, expression of tumor necrosis factor, interleukin-1beta and interleukin-6, and activation of caspase-1, caspase-3 and caspase-11. RESULTS: Postischemic recovery of left ventricular developed pressure, +dP/dt and -dP/dt was significantly increased by p38 MAPK inhibition (MKI) (left ventricular developed pressure: 48.4 +/- 3.87 MKI versus 32.7 +/- 4.32 mm Hg; +dP/dt: 1392.0 +/- 141.7 MKI versus 896.7 +/- 128.5 mm Hg/s; -dP/dt: -889.9 +/- 97.63 MKI versus -548.9 +/- 71.29 mmHg/s). p38 MAPK inhibition also significantly reduced ischemia-reperfusion-induced elevation of left ventricular end-diastolic pressure (82.76 +/- 4.59 MKI vs 69.95 +/- 3.55 mm Hg). p38 MKI decreased myocardial tumor necrosis factor, interleukin-1beta and interleukin-6 protein levels, and reduced active myocardial caspase-1, caspase-3 and caspase-11. CONCLUSIONS: The p38 MAPK pathway indeed mediates the following important events in myocardial apoptosis and functional depression: mitogen-activated protein kinase-activated protein kinase 2, caspase-1, caspase-3 and caspase-11 activation, and tumor necrosis factor, interleukin-1beta, interleukin-6 production after myocardial ischemia. Single site (p38 MAPK) inhibition of these events may have important therapeutic implications in myocardial protection.

Animals↗

PubMed2004

Reduced pericardial levels of endostatin correlate with collateral development in patients with ischemic heart disease.

OBJECTIVES: We investigated whether pericardial levels of a pro-angiogenic factor (vascular endothelial growth factor, VEGF) or an anti-angiogenic factor (endostatin) related to the presence of coronary collateral circulation in patients with significant coronary artery disease (CAD). BACKGROUND: Coronary collateralization favorably alters the prognosis of patients with occlusive CAD. The specific factors that mediate and maintain collateral formation in coronary vessel occlusion are yet to be identified. METHODS: Coronary angiograms from 39 patients undergoing coronary artery bypass surgery were evaluated for the absence of collaterals (n = 20) or the presence of Rentrop classification grade 3 collaterals (n = 19). Pericardial fluid samples were obtained at the time of surgery and were assayed for the VEGF and endostatin by enzyme-linked immunosorbent assay comparing the two groups of patients. RESULTS: Vascular endothelial growth factor levels were not significantly different between the groups (28.86 +/- 4.67 pg/ml vs. 24.39 +/- 3.08 pg/ml, p = 0.43). However, pericardial fluid endostatin levels were nearly 40% lower in patients with grade 3 collateralization compared with those lacking angiographic evidence of collaterals (15.17 +/- 1.87 ng/ml vs. 24.25 +/- 2.08 ng/ml, p < 0.0025). CONCLUSIONS: Pericardial fluid levels of endostatin, but not VEGF, are associated with the presence or absence of collaterals in patients with CAD. These data suggest that the angiogenesis inhibitor endostatin levels may locally modulate coronary collateral formation.

Aged↗

PubMed2004

Hypoxic pulmonary vasoconstriction in cardiothoracic surgery: basic mechanisms to potential therapies.

Hypoxic pulmonary vasoconstriction is postulated to be an adaptive mechanism to match lung perfusion with ventilation; however, the consequences of the maladaptive effects of pulmonary vasoconstriction represent formidable therapeutic challenges. Understanding the basic mechanisms of hypoxic pulmonary vasoconstriction will enhance the assimilation of translational research into clinical practice. The purposes of this review are to (1) define basic mechanisms of pulmonary vasoconstriction and vasorelaxation; (2) delineate the biphasic contractile response to hypoxia; (3) critically examine data that support the mediator hypothesis versus the ion channel hypothesis; and (4) explore potential mechanistic-based therapies for hypoxic pulmonary vasoconstriction.

Adaptation, Physiological↗

PubMed2003

Left anterior descending coronary artery wall thickness measured by high-frequency transthoracic and epicardial echocardiography includes adventitia.

High-frequency, 2-dimensional transthoracic echocardiography (HR-2DTTE) measurements of the left anterior descending (LAD) coronary artery wall thickness are larger than measurements obtained by intravascular ultrasound. We hypothesize that this difference is due to inclusion of the third vascular layer, which may represent adventitia by HR-2DTTE, and that this layer must be increasing in thickness with the development of atherosclerosis. We evaluated the contribution of this third layer to the wall thickness of the normal and atherosclerotic LAD artery imaged by HR-2DTTE using high-frequency epicardial echocardiography (HFEE) as the reference standard. Eighteen patients (10 men, mean age 62 years), 13 with coronary atherosclerosis and 5 with normal coronary arteries, referred for open-heart surgery, underwent preoperative HR-2DTTE evaluation of the LAD artery (SONOS 5500; 3- to 8-MHz transducer) and intraoperative HFEE of the LAD artery (SONOS 5500; 6- to 15-MHz transducer). Wall thickness was greater in patients with coronary atherosclerosis than in those with normal coronary arteries by both HR-2DTTE (1.9 +/- 0.3 vs 1.0 +/- 0.1 mm, p = <0.001) and HFEE (1.8 +/- 0.2 vs 1.0 +/- 0.2 mm, p = <0.001). On HFEE, the average intima plus media thickness was greater in patients with coronary atherosclerosis than in those with normal coronary arteries (0.78 +/- 0.3 vs 0.34 +/- 0.1 mm, p = 0.005). The average thickness of adventitia was also greater in patients with coronary atherosclerosis than in those with normal coronary arteries (0.92 +/- 0.2 vs 0.54 +/- 0.2 mm, p = 0.0005). HR-2DTTE and HFEE measurements of the wall thickness correlated well (r = 0.83 [reader 1], p <0.001; r = 0.61 [reader 2], p <0.01). A third vascular layer, which likely included adventitia, represents a significant portion of the LAD wall thickness imaged by HR-2DTTE and HFEE, and it significantly increases in thickness with the development of atherosclerosis.

Adult↗