mt-tRNAs in the polymerase gamma mutant heart.

Introduction: Mice harboring a D257A mutation in the proofreading domain of the mitochondrial DNA polymerase, Polymerase Gamma (POLG), experience severe metabolic dysfunction and display hallmarks of accelerated aging. We previously reported a mitochondrial unfolded protein response (UPTmt) - like (UPRmt-like) gene and protein expression pattern in the right ventricular tissue of POLG mutant mice. Aim: We sought to determine if POLG mutation altered the expression of genes encoded by the mitochondria in a way that might also reduce proteotoxic stress. Methods and Results: The expression of genes encoded by the mitochondrial DNA was interrogated via RNA-seq and northern blot analysis. A striking, location-dependent effect was seen in the expression of mitochondrial-encoded tRNAs in the POLG mutant as assayed by RNA-seq. These expression changes were negatively correlated with the tRNA partner amino acid's amyloidogenic potential. Direct measurement by northern blot was conducted on candidate mt-tRNAs identified from the RNA-seq. This analysis confirmed reduced expression of MT-TY in the POLG mutant but failed to show increased expression of MT-TP, which was dramatically increased in the RNA-seq data. Conclusion: We conclude that reduced expression of amyloid-associated mt-tRNAs is another indication of adaptive response to severe mitochondrial dysfunction in the POLG mutant. Incongruence between RNA-seq and northern blot measurement of MT-TP expression points towards the existence of mt-tRNA post-transcriptional modification regulation in the POLG mutant that alters either polyA capture or cDNA synthesis in RNA-seq library generation. Together, these data suggest that 1) evolution has distributed mt-tRNAs across the circular mitochondrial genome to allow chromosomal location-dependent mt-tRNA regulation (either by expression or PTM) and 2) this regulation is cognizant of the tRNA partner amino acid's amyloidogenic properties.

Nitric oxide: implications for vascular and endovascular surgery.

Nitric oxide has a key role in vascular homeostasis. It plays a protective role by suppressing abnormal proliferation of vascular smooth muscle following various pathological situations including atherosclerosis and restenosis after vascular interventions such as balloon angioplasty, stent deployment and bypass grafting. It also has strong antiplatelet and anti-thrombogenic properties. In this review, possible applications to daily vascular and endovascular surgery practice, including systemic use of NO donors, enhancing endogenous production of NO by L-arginine and gene therapy, local delivery strategies and coating stents and grafts with NO-delivering/enhancing chemicals are reviewed.

Prevention of intimal hyperplasia by single-dose pre-insertion external radiation in canine-vein interposition grafts.

OBJECTIVES: to evaluate the efficacy of single-dose pre-insertion gamma radiation of vein grafts in the prevention of intimal hyperplasia. METHODS: femoral artery interposition grafts with internal jugular vein were inserted in 12 mongrel dogs. The animals were randomly divided into two groups. Immediately before graft replacement, jugular veins were treated with a single dose of cobalt-60 radiation at 14 Gy or received no radiation (control group). Six weeks after graft insertion, the vein grafts were pressure-perfusion fixed and harvested for the histomorphometric analysis. Quantitative data on anastomotic stenosis were calculated from Gilman parameters after cross-sectional image analysis. RESULTS: vein grafts treated with radiation demonstrated significantly decreased neointima formation compared with grafts in the control group. The mean Gilman parameter for the control group was 1.09 S.E.M. 0.34 mm and for the radiotherapy group was 0.65 S.E. M. 0.23 mm (p<0.05). All vein grafts in the radiotherapy group had a decreased amount of intimal and cellular infiltration. CONCLUSION: single-dose external pre-insertion gamma radiation of vein grafts reduced the amount of intimal hyperplasia in this animal model.

Carotid disease in patients scheduled for coronary artery bypass: analysis of 678 patients.

The purpose of this article is to investigate the frequency of carotid disease and to identify high-risk groups among patients scheduled for isolated coronary artery bypass grafting (CABG) procedures under nonemergent conditions. A total of 678 consecutive patients underwent preoperative carotid artery duplex scanning (CADS) before CABG procedures. Morphology of carotid artery was determined and five groups were formed. Age, sex, cervical bruit, diabetes mellitus (DM), hypertension, smoking, history of cerebrovascular event (CVE), peripheral vascular disease (PVD), and severity of coronary artery disease were investigated to describe the high-risk group for carotid artery disease. In 41% of patients carotid examination produced normal findings; 46.2% had less than 60% luminal stenoses, 7.1% had 60-79% stenoses, 4.6% had 80-99% stenoses, and 1.2% had total occlusion. Previous cerebral ischemic events (CVE) (p<0.05), hypertension (p < 0.01), smoking (p < 0.01), advanced age (p < 0.01), and female sex (p < 0.01) were identified as high-risk factors for carotid artery stenoses. There was a linear association between carotid disease and coronary disease (p < 0.05). Documentation of previous CVE, hypertension, smoking, advanced age, female sex, and severe coronary artery disease may be helpful in identifying patients at high risk for carotid artery stenoses.

Carotid disease is a risk factor for stroke in coronary bypass operations.

The purpose of this study was to investigate the risk of perioperative major cerebrovascular events (MCVEs) in patients undergoing coronary artery bypass grafting (CABG) and to develop preventive therapy. After excluding the patients with marked ascending aortic atheromas and those with combined intracardiac procedures such as valve replacement and aneurysmectomy, 722 consecutive patients who had carotid artery duplex scanning (CADS) and CABG were studied. The results of the study showed the correlation of advanced age, smoking, previous major cerebrovascular event (MCVE), and severe coronary artery disease with high grade carotid artery stenosis of 80-99% (p < 0.05). A total of 13 patients had perioperative MCVE and an analysis of risk factors showed that the MCVE correlated with carotid stenosis of > 60% and reduced cardiac output requiring inotropic support (p < 0.01). Prophylactic carotid endarterectomy (CEA) in patients with 80% to 99% carotid stenosis notably decreased the incidence of MCVE (p < 0.01), and the use of the "pump off" technique instead of standard cardiopulmonary bypass decreased MCVE (p = 0.056). On the basis of these data, prophylactic carotid endarterectomy is effective in averting perioperative MCVE in subjects with carotid stenosis of 80% to 99%, and for those with 60% to 79% carotid stenosis, the pump off technique decreases MCVE.

Spinal cord protection with the use of prostacyclin during aortic occlusion.

This study was planned to investigate if prostacyclin (PGI2) would reduce spinal cord injury following aortic occlusion. Twelve dogs underwent 90 min of aortic occlusion. Six dogs received PGI2 and the remaining animals did not. PGI2 was administered at a dose of 25 ng/kg/min during occlusion of the aorta. There were five paraplegic animals in the control group and one in the PGI2 group 72 hr after aortic occlusion. Neurological recovery was better in the PGI2 group than in the control group (P < 0.05). Malondialdehyde level was 3.55 +/- 0.58 nmole/ml in the PGI2 group and 6.35 +/- 1.27 nmole/ml in the control group 60 min after aortic cross-clamp removal (P < 0.05). At the same time interval, protein thiol groups were 629 +/- 50 micromole/L in the PGI2 group and 376 +/- 69 micromole/L in the control group (P < 0.05). Distal arterial pressure and central venous pressure were 15 +/- 4 and 12 +/- 3 mm Hg in the control group and 33 +/- 5 and 7 +/- 1.6 mm Hg in the PGI2 group, respectively (P < 0.05). In this study exogenously administered PGI2 protected the spinal cord from the hazardous effects of aortic occlusion lasting 90 min.

Hemodynamic effects of acute intestinal ischemia.

Twelve animals entered in this study with the aim of documenting that superior mesenteric artery small occlusions lasting for one hour have adverse effects on the myocardium. Three hours after cross clamp removal CO decreased to 1.07 +/- 0.11 from 1.99-0.09 a preoperative value (p < 0.01) and PCWP increased to 17 +/- 3 from 8 +/- 3 a preoperative value. MOE reduced to 40-5% 3 hours after cross clamp removal. MLE was -0.21 +/- 0.11 three hours after clamp removal. Changes in MOE and MLE were commented as a defect in myocardial aerobic metabolism. As a result of this study it was concluded that toxic mediators are released from the intestine being reperfused after temporary occlusions of the SMA impair myocardial metabolism, resulting in decreased hemodynamic functions.

Routine coronary arteriography before abdominal aortic aneurysm repair.

BACKGROUND: As cardiac complications constitute the principal cause of early and late morbidity and mortality after the surgical treatment of abdominal aortic aneurysm (AAA), a prospective study was planned to evaluate the effects of revascularization of coronary arteries on survival after AAA repair during early and long-term follow-up periods. PATIENTS AND METHODS: A total of 125 patients underwent elective repair of AAA between 1986 and 1994. Coronary arteriography was performed in all cases. All cases with critical left anterior descending artery (LAD) lesions underwent a coronary artery bypass operation either simultaneously or shortly before AAA repair. In addition, percutaneous transluminal coronary angioplasty (PTCA) was performed for symptomatic and critical stenosis of arteries other than the LADs, or if noncritical but symptomatic stenosis of the LADs existed. Early and late follow-up data were obtained for all cases, and late-term cumulative survival rates were calculated. RESULTS: Coronary artery lesions were found in 66 (53%) cases. In 24 cases, AAA repairs were performed 2.3 (mean) months after coronary artery bypass grafting (CABG), whereas in 4 cases both procedures were performed simultaneously. PTCA was performed in 4 cases 3 to 4 days prior to the abdominal surgery. Even though the coronary artery lesions were found inoperable in 7 cases, these patients underwent repair of AAA because of rapidly expanding and painful aneurysms. Early mortality rate was 4% (5 cases), in which 3 of these were from the group inoperable for CABG. A mean follow-up of 3.17 years (3 to 87 months) was achieved for all discharged patients. Cumulative survival rates for 6 months and 1, 2, 3, and 6 years were 99%, 99%, 95%, 93%, and 89%, respectively. CONCLUSIONS: The results of this study emphasize the importance of coronary artery revascularization for early, and especially for late, survival after AAA repair.

Vascular complications related to percutaneous insertion of intraaortic balloon pumps.

The hemodynamic effects of intraaortic balloon pumps (IABPs) are well known. The use of IABPs is prone to many complications, including those classified as vascular. These complications are said to be more frequent with percutaneous insertion techniques. These complications and the algorithm for identifying patients who are most likely to suffer vascular complications were evaluated in a retrospective manner in a group of patients that received percutaneous IABPs. The study group consisted of 449 patients. The mean age of these patients was 53.6 +/- 12.8 years (range, 18 to 80 years), and 24.7% were female. The early mortality rate of these patients was 53.2%. The mortality for patients in whom vascular complications developed was significantly higher than that in the patients who did not suffer any vascular complications (65.7% versus 50.8%; p = 0.018). Minor or major vascular complications developed in 17.4% (n = 78) of the patients. There was no statistical difference in the frequency of complications between the patients who received a sheathless IABP and those who received a sheathed IABP. Ischemic complications occurred in 16.6% of the patients who received a sheathless IABP and in 17.6% of the patients with sheathed IABPs (p < 0.05). Diabetic patients (relative risk, 2.5), female patients (relative risk, 1.83), patients with peripheral vascular disease (relative risk, 3.69), and patients undergoing coronary artery bypass operations (relative risk, 2.08) were at increased risk for suffering vascular complications. These risk factors should be evaluated before insertion of an IABP, and routes other than percutaneous femoral insertion are preferred if the patient is IABP dependent.

Effects of prostacyclin on spinal cord ischemia: an experimental study.

BACKGROUND: Paraplegia after thoracic aortic aneurysm has an incidence of 2.2% to 24%. This study was planned to show the beneficial effects of prostacyclin on spinal cord ischemia. METHODS: Twelve rabbits underwent 30 minutes of aortic occlusion. Six rabbits received prostacyclin, whereas the remaining rabbits did not. Prostacyclin administration was started with a rate of 5 ng/kg/min 5 minutes before aortic occlusion. This dosage was increased to 25 ng/kg/min during aortic occlusion. Prostacyclin administration after aortic occlusion was maintained for a period of 5 minutes. During this period, prostacyclin dosage was 5 ng/kg/min. RESULTS: One rabbit in the prostacyclin group and five rabbits in the control group were paraplegic. Arterial pressure proximal to the clamp was 65 +/- 7 mm Hg before aortic occlusion and 78 +/- 10 mm Hg during aortic occlusion in the control group and 68 +/- 12 mm Hg before aortic occlusion and 65 +/- 6 mm Hg during aortic occlusion in the prostacyclin group. Arterial pressure distal to the clamp was 11 +/- 4 mm Hg during aortic occlusion in the control group and 18 +/- 5 mm Hg during aortic occlusion in the prostacyclin group (p = 0.02). CONCLUSIONS: Intravenous prostacyclin reduced the neurologic injury caused by spinal cord ischemia and reperfusion after 30 minutes of aortic occlusion in the rabbit model.

Pseudoaneurysm of the tibioperoneal trunk.

A young woman with an iatrogenic coagulation defect related to a mechanical mitral valve prosthesis developed a pseudoaneurysm of the tibioperoneal trunk after a minor blunt injury. The importance of minor blunt trauma in such cases and the surgical approach are reviewed.

Surgical approach to pseudoaneurysms with Behçet's disease.

One of the arterial complications of Behçet's disease, arterial false aneurysms, has a sudden onset of symptoms and high mortality risk if left untreated. Four cases with arterial pseudoaneurysms of 3 male patients is reported and the choice of surgical intervention is emphasized. It is underlined that PTFE grafts are the graft of choice in reconstructions for arterial complications of Behçet's disease.

Bilateral triple renal arteries in a patient with iliac artery occlusion: a case report.

Multiple renal artery abnormalities in a surgical patient with iliac artery occlusion is presented in this case report. Angiographic and operative appearance has been reviewed. We found three renal arteries bilaterally. This abnormality has been compared with the literature and the clinical importance has been emphasized.

A simple infusion method for measurement of intraoperative peripheral vascular runoff resistance.

A simple infusion system to assess the status of distal runoff was investigated on both hindlimbs of five mongrel dogs. Infusion catheters were placed in the superficial femoral arteries and the origin of the lower leg arteries was exposed for anatomic manipulation of the distal runoff. Saline solution was infused through the superficial femoral arteries at 64, 129, and 193 cm levels to calculate volume flow and index of resistance to flow. The in vitro part of the study was undertaken to analyze the effect of different-size catheters on flow rates in a rigid undistensible model. In the hindlimb study the flow differed significantly between two- and one-vessel runoff status at 50 and 100 mm Hg infusion pressures. In the in vitro study, in contrast to the hindlimb study, index of resistance to flow values for different-size catheters remained almost unchanged as the infusion pressure increased, demonstrating the distensibility of the runoff bed in dogs. A preliminary clinical study in 13 patients undergoing infrainguinal bypass surgery demonstrated a good correlation between angiographic runoff evaluation and intraoperative flow values. Valuable information can be obtained about the status of the distal runoff by this simple infusion method, which might be used to improve the prediction of outcome of infrainguinal bypass surgery.

The association of lower extremity peripheral vascular disease in patients undergoing coronary bypass surgery.

The association of lower extremity peripheral vascular disease (PVD) in patients undergoing coronary artery bypass (CAB) has been studied in two groups of patients who have been operated upon between January and May 1987. Group 1 consists of 125 cases in which only resting ankle-arm pressure index (AAPI) were evaluated. Group 2 consists of 50 cases where both resting and after exercise AAPI were recorded. In total, 17 cases of one extremity and in 10 both lower extremity resting AAPI were below 0.9 (15.4%). In Group 2 comparison of resting and after exercise AAPI on both sides showed no statistically significant difference. However in Group 2, 13 cases (26%) had after exercise AAPI below 0.9 and in 26 (52%) cases after exercise AAPI were lower than the resting AAPI. This study showed that, although the coexistence of PVD in patients undergoing CAB is not as high as the coexistence of CAD in patients undergoing peripheral vascular procedures, this percentage can increase when the presence of PVD is evaluated with an exercise test whenever possible.