We have reported that cardiac preconditioning against ischemia-reperfusion (IR) can be induced by transient ischemia (TI) and alpha 1-adrenoreceptor stimulation, both mediated by protein kinase C (PKC) (Mitchell, M., X. Meng, C. Parker, E. Brew, A. Harken, and A. Banerjee. Circ. Res. 76: 73-81, 1995). Our study objective was to explore the mechanism of endogenous preconditioning and address the role of PKC activation in bradykinin-mediated cardiac functional protection. Isolated rat heart was used to assess the effects of exogenous bradykinin, TI, selective B2-receptor blocker, and PKC antagonism on cardiac functional recovery after a global IR injury. Final recovery of developed pressure was improved in hearts treated with bradykinin and TI compared with controls. Bradykinin- and TI-mediated preconditioning was eliminated with coinfusion of the B2-receptor antagonist. Further evaluation of bradykinin-mediated preconditioning revealed that PKC blockade also eliminated functional protection. Immunofluorescent stains of bradykinin-treated hearts demonstrated translocation and activation of specific PKC isoforms in the preconditioned heart. We conclude that TI-mediated preconditioning involves intrinsic cardiac bradykinin receptor stimulation. Bradykinin, through the B2 receptor, initiates a series of intracellular events culminating in the activation of PKC.
Despite national consensus of PAD as a CAD equivalent, patients are currently undertreated with regard to atherosclerotic risk factor modification. Until broader recognition of this disease process exists, vascular surgeons must continue to champion medical as well as surgical treatments for these patients.
The signal transduction of ischemic preconditioning involves activation of endogenous receptor-based systems, including alpha 1-adrenoceptors and adenosine receptors. Whereas preconditioning protects against ischemia-reperfusion injury, it is unknown whether this protective strategy might be useful clinically. Furthermore, human atrium has been successfully preconditioned, but it is unknown whether human ventricle can be functionally protected against hypoxia-reoxygenation. To study these questions, isolated rat ventricle and human ventricular trabeculae were suspended in an organ bath and subjected to 30 min of hypoxia and 60 min of reoxygenation. In the rat ventricle, preconditioning was induced by 5 min of rapid pacing at 3 Hz in hypoxic buffer without glucose (simulated ischemia), alpha 1-adrenoceptor stimulation (phenylephrine), or adenosine receptor stimulation (adenosine). In the human trabeculae the effects of preceding simulated ischemia and alpha 1-adrenoceptor and adenosine receptor stimulation were examined against hypoxia-reoxygenation. In the rat, pretreatment with simulated ischemia and alpha 1-adrenoceptor and adenosine receptor stimulation improved recovery of developed tension (56 +/- 3, 56 +/- 4, and 58 +/- 2%, respectively) compared with control trabeculae (25 +/- 2%) after hypoxia-reoxygenation (P < 0.05). In human trabeculae, simulated ischemic preconditioning and alpha 1-adrenoceptor and adenosine receptor stimulation augmented recovery of developed tension (65 +/- 5, 59 +/- 6, and 60 +/- 3%, respectively) compared with control (29 +/- 2%) after hypoxia-reoxygenation (P < 0.05). We conclude that functional cardioadaptation (preconditioning) against hypoxia-reoxygenation injury in rat and human myocardium exists and that alpha 1-adrenergic and adenosine receptor signaling participate in conferring this protection.
Transfemoral endovascular repair of abdominal aortic aneurysms (AAAs) has proven feasibility and considerable benefits over traditional open repair. 1-3 However, strict anatomic requirements have limited the application of this method of therapy. Indeed, several recent studies suggest that only 10% to 20% of all AAAs are treatable with currently available commercial devices. 4-6 Although inadequate proximal aortic neck length and diameter are generally thought to be the main limitations in endograft placement, adverse iliac anatomy precludes placement in as many as 50% of patients. 5 The use of an aortouniiliac endoprosthesis in combination with a femorofemoral crossover graft would permit an endovascular approach to the broadest array of patients as only one iliac system is required to satisfy anatomic criteria (Fig 1, A). However, enthusiasm for this type of reconstruction has been restrained by apprehension regarding the durability of the femorofemoral bypass graft and the potential for late complications such as graft infection or pseudoaneurysm formation. Furthermore, the consequences of exclusion of one or both internal iliac arteries Utility and reliability of endovascular aortouniiliac with femorofemoral crossover graft for aortoiliac aneurysmal disease Objective: The purpose of this study was to determine the early efficacy of endovascular aortouniiliac stent grafts with femorofemoral bypass graft in the treatment of aortoiliac aneurysmal disease. Methods: We analyzed 51 consecutive patients from January 1997 to March 1999 with a mean follow-up of 15.8 months. Patients ranged in age from 44 to 93 years (mean, 75 years) with a mean aortic aneurysm diameter of 6.2 cm. Technical success was achieved in 50 patients; one patient required conversion to open repair intraoperatively. We placed 28 custom-made and 22 commercial devices. The mean operative time was 223 minutes. The endograft was extended to the external iliac artery in 42% of cases. The contralateral common iliac artery was occluded using either a closed covered stent or intraluminal coils. Results: The median hospital stay was 4 days with an average intensive care unit stay of 0.25 days. There were no operative mortalities. Two patients died during follow-up from unrelated conditions. Endoleaks occurred in 11 patients (22%); seven patients (14%) required intervention (four catheter based, three operative). Other complications occurred in 38% of patients but were largely remote or wound related. One femorofemoral bypass graft occluded immediately postoperatively as a result of an intraprocedural external iliac dissection yielding a 98% primary patency and 100% secondary patency. Clinical success was achieved in 88% of patients. Conclusions: These data suggest that this strategy represents a reliable method of repair of aortoiliac aneurysmal disease and extends the capability of an endoluminal approach to patients with complex iliac anatomy. (J Vasc Surg 2000;31:1135-41.)
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