Vascular pulsations stimulating nitric oxide release during cyclic exercise may benefit health: a molecular approach (review).

It is widely assumed that all exercise, regardless of the degree of difficulty or strenuousness, is good (no pain-no gain). In this speculative review of the literature and our research findings we highlight the fact that strenuous exercise taken to the extreme initiates an immune and vascular proinflammatory situation. However, mild cyclic exercise appears to produce health benefits for an individual. In part, this is due to vascular cyclic pulsations, occurring in mild exercise, stimulating constitutive nitric oxide synthase derived nitric oxide release. This in turn down-regulates vascular endothelial cells and immunocytes, as well as their interaction and inhibits the disassociation of NF-kappaB, preventing the production of proinflammatory cytokines. The nitric oxide so generated may even scavenge excess free radicals, preventing tissue damage. Prolonged strenuous exercise appears to limit these positive phenomena because of the maintained and prolonged high blood pressure that reduces the cyclic pulsations, limiting nitric oxide production. We further note that pathological conditions, i.e., Parkinson's disorder, may benefit from mild exercise, i.e., cyclic nitric oxide production, since the inactivity associated with this disease may lead to compromised nitric oxide production, initiating a progressive deterioration of tissues, including peripheral adrenergic neurons, due to a lack of adequate basal nitric oxide levels required to maintain the vascular microenvironment in a mild state of inhibition. We conclude that mild exercise represents an alternate and economical therapy to preserve health and/or diminish the rate of decline of the normal physiological processes that may even be associated with aging.

A decade of experience with the glutaraldehyde-tanned human umbilical cord vein graft for revascularization of the lower limb.

Between October 1975 and November 1985, 907 lower limb bypasses were constructed in 715 patients (799 limbs) with glutaraldehyde-stabilized umbilical veins (UV-G) used as the predominant, or sole, graft material. Each reconstruction was classified in one of eight categories depending on the site of the distal anastomosis: above- and below-knee popliteal, anterior and posterior tibial, peroneal, trifurcation, sequential, and crural (tibial or peroneal) bypasses with adjunctive distal arteriovenous fistulas. Primary and secondary cumulative graft patency rates were determined for each category as well as cumulative actual palliation that combines end points of graft failure, amputation, and death. Half-life patencies for popliteal, tibial, and peroneal bypasses were 6.5, 2.3, and 1.7 years, respectively. Perioperative graft thrombosis occurred in 11% of popliteal reconstructions compared with 22% for the crural group. Nonocclusive graft failure caused by infection, aneurysm, or progressive foot gangrene occurred in 87 grafts (8%). The overall infection rate was 4.3%. Anastomotic aneurysms (1.4%) and strictures (2.1%) occurred infrequently as isolated phenomena. The incidence of graft dilatation and aneurysms assumed significant proportion after 5 years (36% aneurysms and 21% dilation); the diagnosis was particularly facilitated by B-mode imaging. Nevertheless, the overall clinical impact of graft degradation remained minimal (6% after 5 years). Twenty-two of 26 graft aneurysms were excised with successful graft replacement achieved in 10. During this 10-year period, our attitudes did change with regard to the indication for UV-Gs in relation to the maturation of infrapopliteal reconstructive surgery, appreciation of the superior results attainable with in situ saphenous vein, recognition of morphologic changes in long-term UV-G implants, and the growing documentation of poor results with polytetrafluorethylene in the crural position. We believe that UV-G is an acceptable alternative to the absent or deficient autologous vein, particularly in patients with limited life expectancy and where expediency may be a critical factor.

Biodegradation and aneurysm formation in umbilical vein grafts. Observations and a realistic strategy.

In a series of 756 glutaraldehyde-stabilized umbilical vein grafts implanted over a 7 1/2-year period, aneurysms were identified in seven cases. The earliest aneurysm was seen at 31 months after implantation and the remainder between 43 and 79 months after surgery. Corrective surgery was performed in five cases and succeeded in four. Although definite mechanisms have not been identified, mechanical fatigue, reversal of aldehyde crosslinks, and immunologic factors may be operative. The pathologic changes include: (1) actual dilation of both graft and mesh with or without intraluminal thrombus and, (2) maintenance of graft diameter with erosion of the umbilical vein and polyester mesh rupture leading to perigraft hematoma and false aneurysm formation. Microscopic examination and infrared spectral analysis confirmed the presence of host-contributed lipid in some specimens. Although this is a low incidence of aneurysm formation, umbilical vein grafts should be selected primarily for patients with limited life expectancy or for whom alternative materials with comparable or superior patency rates are not available or acceptable. Periodic angiography, particularly after 3 or 4 years, is recommended as a routine part of follow-up examinations. Improved graft materials and control of host environmental factors are potential means to reduce the noted degradation.

Distal arteriovenous fistula as an adjunct to maintaining arterial and graft patency for limb salvage.

Sixty-one distal arteriovenous fistulas (dAVFs) were constructed as adjuncts to tibial and peroneal vascular reconstructive procedures in 58 patients threatened with imminent limb loss. Specific indications for dAVF construction were absent or deficient pedal arches, usually associated with small, calcareous crural vessels. Conventional bypasses had been previously performed in 35 patients. Cumulative graft patency rates were 56%, 39%, and 18% at 6, 12, and 24 months, respectively. For the same intervals, the figures were 56%, 52%, and 52% (P less than 0.001 at 24 months) for nonAVF reconstructions (n = 49). The corresponding cumulative limb salvage rates were 62%, 52%, and 40% for the dAVF group and 78%, 72%, and 72% for the nonAVF group (P less than 0.05 at 24 months). The perioperative mortality rate was 7% (four of 61). Twenty-four amputations were required, of which 16 were below the knee and six despite patent grafts. There was no significant morbidity attributable directly to the dAVF. Cardiac output showed no deviations from normal values. Primary causes of early failure were infection (n = 4), absence of satisfactory veins (n = 6), and inappropriate case selection (n = 7). Intimal hyperplasia led to dAVF closure and graft failure in 13 patients. This study shows that dAVFs can maintain graft patency by diversion of the overload on a high-resistance vascular bed and, secondarily, by augmentation of inflow. Immediate survival of the limb still depends on the arterial runoff, as retrograde venous flow caused by venous valvular incompetence is a delayed development. Adjunctive dAVF is justified in selected cases where conventional bypass failure has occurred or is predictable by increased pedal vascular resistance.

Influence of failed vascular bypass procedures on conversion of below-knee to above-knee amputation levels.

From 1975 to 1980, 79 major limb amputations were performed from a group of 552 lower extremity vascular reconstructions with glutaraldehyde-stabilized umbilical vein grafts. All amputations were performed in instances in which limb salvage had been the indication for the attempted bypass (n = 520)--an incidence of 15.2%. Twelve of 51 below-knee (BK) amputations were converted to above-knee (AK) levels (crude failure rate, 23.5%). The highest crude failure rate occurred after failed bypass to the popliteal artery (33.3%); the lowest occurred after failed tibial bypass (16.7%), and the peroneal arteries were intermediate (22.2%). In addition to these 12, 28 primary AK amputations were performed. Excluding nine cases judged to require AK amputations before the attempted vascular reconstruction, success/failure rates for the entire series and each of the reconstruction types were calculated. Success, defined as a healed BK stump, occurred least after failed popliteal bypass, 44.5%, compared to 71.4% and 53.8% for the tibial and peroneal groups, respectively. Thus, failure of a popliteal bypass was more apt to lead to an AK amputation (56.5%) than failure of a distal bypass. In fact, tibial bypass failure leading to an AK stump occurred at a frequency (28.6%) almost similar to that obtained by other investigators when no previous bypass had been performed. Comparative cumulative graft patency and limb salvage rate data confirm the value of reconstructive vascular surgery, particularly in the peroneal group where negativism with regard to its clinical usefulness persists. With improved case selectivity and surgical expertise, increasing limb salvage rates can be secured while minimizing the definite morbidity of conversion of BK to AK amputation with failed vascular bypass.

Tibial arteriovenous fistula: successful use for limb salvage.

Embolization of atheromatous material from abdominal aortic aneurysms to the distal arterial circuit is a well-recognized clinical entity causing the "blue toe syndrome." A case is presented in which this phenomenon resulted in obliteration of the pedal arch and thrombosis of the tibial arteries. As a result, forefoot gangrene, severe leg ischemia and anterior and posterior compartment syndromes occurred. Salvage of the extremity required an extraordinary approach with the construction of an arteriovenous fistula between the posterior tibial vessels. The literature on the use of therapeutic and adjunctive arteriovenous fistulas and their physiology is discussed.

Morphologic structure of the pedal arch and its relationship to patency of crural vascular reconstruction.

Pedal arch integrity can be determined morphologically and functionally. The former is accessible by contrast studies and intraoperative catheterization, the latter, by flow studies and observation of graft patency. The roengten image of an intact pedal arch corresponds to the anatomic plantar arch. Sixty-four arch studies obtained by adequate intraoperative arteriography were categorized as intact, deficient or inadequate or absent. Patency of crural reconstructions was obtained in 18 of 24 patients with intact arches as compared with 15 of 32, p<0.06, when the arch was deficient. Crural reconstruction in the face of an inadequate or absent arch resulted in predictable graft closure. Qualitative factors, that is, size, calcium and stenotic lesions, are integrally related to over-all graft performance even with intact arches. The deficient arch for tibial and peroneal reconstruction continues as a challenge to the vascular surgeon.

Remote profunda femoral bypass for limb salvage.

Patients with patency of the distal segment of the profunda femoral arteries can be subjected to a direct end-to-side bypass with either tissue or synthetic grafts to increase blood flow to the lower extremity. The effectiveness and durability of this procedure will be enhanced by patency of the popliteal artery. Diffuse profunda femoris disease, popliteal or tibial peroneal obliterative disease and gangrenous lesions tend to militate against the success of this operation as an isolated procedure without augmenting flow to the distal part of an artery in the leg. Of 18 remote profunda femoris bypasses performed during a four year period, early amputation was required in two patients because of inadequate distal flow and the inability to establish downstream reconstruction. In one patient, an early bypass to the peroneal artery was required following closure of the profunda femoris bypass. The remaining 15 bypasses resulted in limb salvage and significant relief of symptoms. Three patients subsequently required secondary downstream reconstructions. The profunda femoris is surgically accessible for a long length and can serve as an adequate source of blood to the leg and foot in selected patients.

Adjunctive arteriovenous fistula with tibial and peroneal reconstruction for limb salvage.

Arteriovenous fistulas were constructed as an adjunct to femoral peroneal and tibial bypasses in 13 patients threatened by imminent limb amputation. Previous attempts at conventional vascular reconstructive procedures had failed in nine patients. Deficient or absent pedal arches were noted in all patients, as were poor quality or small crural arteries. Graft patency was achieved in 11 cases and limb salvage in 10. There was no mortality. A steal phenomenon occurred in one patient and was successfully treated by secondary popliteal vein ligation. These preliminary results clearly indicate that an adjunctive arteriovenous fistula can maintain patency in a femoral tibial or peroneal bypass graft while preserving flow into the markedly diseased distal circulation.

Remote hydraulic syringe actuator: its use to avoid radiation exposure during intraoperative arteriography.

A simple, inexpensive device consisting of a double hydraulic syringe system and a holding fixture was devised for intraoperative arteriography to avoid exposure of personnel to radiation. The procedure of intraoperative angiography has thus become safer, less time consuming, and more reliable in obtaining high-quality angiographic studies.

Synchronous aortofemoral or iliofemoral bypass with revascularization of the lower extremity.

Bypassing aortoiliac stenosing lesions to the profunda femoria alone, even with extensive end-arterectomy and angioplasty of the latter, will not provide predictable excellent results in the presence of gangrene and occlusion in the femoral popliteal system. With severe pregangrene and rest pain, residual ischemic complaints are also common, and if lesions are present, healing is incomplete or, at best, delayed. Alternatively, femoropopliteal or tibial bypass, in the presence of even moderately diminished inflow, is subject to either early or delayed closure, unless proximal repair is also performed in appropriately selected patients. Synchronous correction of tandem lesions involving the aortoiliac and femoropopliteal segments should, therefore, be considered for limb salvage only and particularly in the presence of focal gangrene, excision or debridement of which can be anticipated to heal after successful bypass. Major diminution in femoral inflow usually indicates the need for proximal repair only, even in the presence of distal lesions. Noninvasive studies and intraoperative flow determinations are not uniformly helpful in patient selection. Synchronous aortofemoral or iliofemoral and femoropopliteal or tibial reconstructions were performed upon 38 patients, 15 of whom had no prior vascular operation and 23 of whom had previously undergone either aortofemoral or femoropopliteal bypasses that had failed. Graft patency for all patients was 76 per cent, and although it was better for the patients in group 1 than for those in group 2, no statistical significance existed between the two groups. Improved patient selection and criteria for performing synchronous reconstructions might originally have been of benefit for the patients in group 2, avoiding more difficult secondary repairs. It must be emphasized, however, that synchronous reconstructions should not be done routinely in the presence of multilevel disease. Rather, specific indications do exist and should be considered on an individual basis.

The role of the peroneal artery for limb salvage.

Peroneal artery revascularization was performed in 61 cases for limb salvage and compared to a comparable group of 89 tibial artery reconstructions. Preoperative arteriography is essential to define runoff quality and pedal arch integrity. Intraoperative arteriography and flow determinations minimize failures due to technical error and provide some indication of the prognosis for graft patency. Failure to augment flow by at least 50% suggests pedal arch deficiency and is predictive for early graft closure. Cumulative patency for peroneal bypass was 55 +/- 8% at 1 year and 38 +/- 10% at 30 months compared to 63 +/- 6 and 59 +/- 7% for tibial reconstructions at the same time intervals. Most graft failures occurred within the first six months. Nineteen peroneals have been followed for more than one year with only three failures occurring. Improved criteria for case selection resulted in an 80% decrease in the number of failed grafts for the second half of this series. A similar reduction was noted for secondary operations. Results obtained with good quality saphenous veins (37 +/- 13% at 30 months) and glutaraldehyde tanned umbilical veins (53 +/- 11%) depend more on technical, pathologic and biologic factors than on the particular graft material employed. The mortality rate at 30 days was 3.3% and compared favorably with other limb salvage procedures and with primary amputations. Cumulative patient survival with functional limbs was 79 +/- 9% at 30 months and was distinctly superior to reported data on survival of amputees. A cumulative limb salvage rate of 79 +/- 6% at 30 months for the peroneal group makes such reconstructions definitely favorable to uniform limb ablation.

Evaluation of intraoperative arteriography as a routine for vascular reconstructions.

A retrospective analysis of 391 intraoperative arteriograms performed after reconstruction operations on the carotid, aorta and lower extremity vasculature showed the value of incorporating this procedure as a routine only for the last mentioned site. Identification and correction of inadequacies due to technique are possible. Revisions in technique based upon these experiences have significantly diminished their incidence. Routine intraoperative arteriography for revascularization procedures of the lower extremity has further enabled us to classify reliably the runoff and correlate these findings with subsequent graft patency. Late graft closure, predominantly due to progressive or accelerated obliterating atherosclerosis in the distal circulation, occurred almost exclusively within the first year following reconstruction in those patients identified as having poor runoff by intraoperative arteriography. This group, in particular, should be closely monitored by noninvasive physiologic means and even post-operative arteriography to enable either prophylactic or therapeutic correction. In some instances, based upon intraoperative arteriography or subsequent studies, fruitless and potentially harmful reoperative vascular procedures may be obviated.

Evaluation of glutaraldehyde-tanned human umbilical cord vein as a vascular prosthesis for bypass to the popliteal, tibial, and peroneal arteries.

One hundred and thirty-one reconstructions to the popliteal (n = 80), tibial (n = 26), and peroneal (n = 25) arteries were performed using glutaraldehyde (GA)-tanned human umbilical cord veins. Cumulative patency rates to 20 months, calculated by the standard life-table method were 84.8%, 74.0%, and 49.6% for popliteal, tibial, and peroneal reconstructions, respectively. The latter included many of the early cases with extremely advanced obliterative atherosclerosis and gangrene. These results are equivalent and even superior to those obtained with saphenous veins, particularly when the cases are analyzed in distinct clinical and pathological categories. The quality of the runoff was the major determinant in obtaining long-term patency and limb function. The primary factor accounting for graft closure was progression of the atherosclerotic process in the distal circulation. No failures could be attributed directly to the graft. This clinical experience confirmed previous data showing the unique properties of the GA-tanned umbilical vein. It is anticipated that longer-term follow-up will continue to show the superior qualities of this new vascular substitute.