Topical Application Of Papaverine Research Articles

Combined effect of left stellate ganglion blockade and topical administration of papaverine on left internal thoracic artery blood flow in patients undergoing coronary revascularization.

Background:Left stellate ganglion blockade (LSGB) may have additive effect to topical administration of papaverine on prevention of vasospasm of left internal thoracic artery (LITA).Aims:This study aims to compare LITA blood flow with topical application of papaverine alone or in combination with LSGB.Setting:Tertiary care hospital.Design:Prospective randomized controlled study.Materials and Methods:A total of 100 patients operated for coronary revascularization were randomly and equally allocated into two groups. In control Group-C, papaverine was applied topically during the dissection of LITA. In Group-S, the additional LSGB was performed. Blood flow was measured from cut end of the LITA for 15 s. Primary objectives of the evaluation were to observe differences in the LITA blood flow. Observing incidence of radial-femoral arterial pressure difference after cardiopulmonary bypass (CPB) was secondary objective.Statistical Analysis:Student's unpaired t-test and Fisher's exact test to find out a significant difference between the groups.Results:LITA flow in Group-S was insignificantly more (49.28 ± 7.88 ml/min) than Group-C (47.12 ± 7.24 ml/min), (P = 0.15). Radio-femoral arterial pressure difference remained low for 40 min after termination of CPB in the Group-S compared to the Group-C (−0.99 ± 1.85 vs. −1.92 ± 2.26).Conclusion:Combining LSGB with papaverine does not increase the LITA blood flow compared to when the papaverine is used alone. However, ganglion blockade reduces radial-femoral arterial pressure difference after CPB. Blockade can be achieved successfully under the ultrasound guidance without any complications.

Anterograde Intra-Arterial Urokinase Injection for Salvaging Fibular Free Flap

We present a case of a 57-year-old male patient who presented with squamous cell carcinoma on his mouth floor with cervical and mandibular metastases. Wide glossectomy with intergonial mandibular ostectomy, and sequential reconstruction using fibular osteomyocutaneous free flap were planned. When the anastomosis between the peroneal artery of the fibular free flap and the right lingual artery was performed, no venous flow was observed at the vena comitans. Then re-anastomosis followed by topical application of papaverine and lidocaine was attempted. However, the blood supply was not recovered. Warm saline irrigation over 30 minutes was also useless. Microvascular thromboses of donor vessels were clinically suspected, so a solution of 100,000 units of urokinase was infused once through a 26-gauge angiocatheter inserted into the recipient artery just at the arterial anastomotic site, until the solution gushed out through the flap vena comitans. Immediately after the application of urokinase, arterial flow and venous return were restored. There were no complications during the follow-up period of 11 months. We believe that vibrating injuries from the reciprocating saw during osteotomies and flap insetting might be the cause of microvascular thromboses. The use of urokinase may provide a viable option for the treatment of suspicious intraoperative arterial thrombosis.

Transient oculomotor nerve palsy after topical administration of intracisternal papaverine

Dear Editor, We present three patients who suffered aneurysmal subarachnoid hemorrhage with mean age of 48 years. Two patients had middle cerebral artery aneurysms and the third had an anterior communicating artery aneurysm. All three patients underwent a standard frontotemporal craniotomy for clipping of ruptured aneurysm. All three aneurysms were clipped without the need for temporary occlusion and, in no case, was dissection or direct visualization of the oculomotor nerve necessary to obtain proximal control. Local vasospasm was visually apparent in the exposed carotid circulation in all three cases; thus topical 3–5 cc of a 3% solution of papaverine was administered after surgical clipping was completed. Immediate postoperative exam in all three cases revealed isolated ipsilateral oculomotor nerve palsy. The patients had no other neurological deficits suggestive of a space-occupying lesion or raised intracranial pressure. An immediate postoperative CT head was performed (Fig. 1) that only revealed expected postoperative changes and some intracranial air. In all three patients, the deficit resolved completely within a 24-h period (range 3–24 hours). Further recovery was uneventful and all three of these patients were discharged home without focal neurological deficit. Papaverine is a natural heterocyclic nitrogen alkaloid found in opium. It is a commonly used vasodilator that acts directly on smooth muscle. Based on clinical and experimental data, topical application of papaverine for reversal of vasospasm was first advocated by Pool in 1958 [8, 9]. Since then, papaverine has been used by neurosurgeons topically when encountering intraoperative visual evidence of vasospasm [3, 10]. There have been isolated case reports of facial nerve palsies [2, 6, 7], auditory nerve palsy [1], and pupillary changes [3, 10]. Although it may be common knowledge, a review of literature did not yield any prior reports of transient oculomotor nerve palsy (TONP) after topical/intracisternal papaverine use. Transient oculomotor nerve palsy after surgical clipping for aneurysms occurs in 2.9% to 32% of cases depending on the location of the aneurysm. In many cases, the phenomenon has been attributed to traction, mechanical irritation, or transient loss of blood supply to the oculomotor nerve [4, 5]. In our cases, the TONP was seen in the absence of any of the known risk factors. No manipulation of or dissection around the oculomotor nerve was performed in our three cases. Since these cases were observed, we have introduced a practice change by diluting the 3% papaverine solution to 0.3% with normal saline. In our experience, such dilution leads to satisfactory reversal of arterial spasm while preventing the transient oculomotor nerve palsies. Mechanistic explanation of the mode of action of papaverine in causing TONP is unknown. Animal studies combined with in vitro analysis of the mechanisms of action of papaverine are needed to further elucidate this important effect. Further prospective studies are needed to P. Chittiboina :A. Nanda :B. Guthikonda (*) Department of Neurosurgery, LSUHSC Shreveport, P O Box 33932, Shreveport, LA 71130-3932, USA e-mail: bguthi@lsuhsc.edu

Transient facial nerve palsy after topical papaverine application during vestibular schwannoma surgery

✓Some evidence in the literature supports the topical application of papaverine to the cochlear nerve to prevent internal auditory artery vasospasm and cochlear ischemia as a method of enhancing the ability to preserve hearing during acoustic neuroma surgery. The authors report a case of transient facial nerve palsy that occurred after papaverine was topically applied during a hearing preservation acoustic neuroma removal. A 58-year-old woman presented with tinnitus and serviceable sensorineural hearing loss in her right ear (speech reception threshold 15 dB, speech discrimination score 100%). Magnetic resonance imaging demonstrated a 1.5-cm acoustic neuroma in the right cerebellopontine angle (CPA). A retrosigmoid approach was performed to achieve gross-total resection of the tumor. During tumor removal, a solution of 3% papaverine soaked in a Gelfoam pledget was placed over the cochlear nerve. Shortly thereafter, the quality of the facial nerve stimulation deteriorated markedly. Electrical stimulation of the facial nerve did not elicit a response at the level of the brainstem but was observed to elicit a robust response more peripherally. There were no changes in auditory brainstem responses. Immediately after surgery, the patient had a House–Brackmann Grade V facial palsy on the right side. After several hours, this improved to a Grade I. At the 1-month follow-up examination, the patient exhibited normal facial nerve function and stable hearing. Intracisternal papaverine may cause a transient facial nerve palsy by producing a temporary conduction block of the facial nerve. This adverse effect should be recognized when topical papaverine is used during CPA surgery.

Transient facial nerve palsy after topical papaverine application during vestibular schwannoma surgery

Some evidence in the literature supports the topical application of papaverine to the cochlear nerve to prevent internal auditory artery vasospasm and cochlear ischemia as a method of enhancing the ability to preserve hearing during acoustic neuroma surgery. The authors report a case of transient facial nerve palsy that occurred after papaverine was topically applied during a hearing preservation acoustic neuroma removal. A 58-year-old woman presented with tinnitus and serviceable sensorineural hearing loss in her right ear (speech reception threshold 15 dB, speech discrimination score 100%). Magnetic resonance imaging demonstrated a 1.5-cm acoustic neuroma in the right cerebellopontine angle (CPA). A retrosigmoid approach was performed to achieve gross-total resection of the tumor. During tumor removal, a solution of 3% papaverine soaked in a Gelfoam pledget was placed over the cochlear nerve. Shortly thereafter, the quality of the facial nerve stimulation deteriorated markedly. Electrical stimulation of the facial nerve did not elicit a response at the level of the brainstem but was observed to elicit a robust response more peripherally. There were no changes in auditory brainstem responses. Immediately after surgery, the patient had a House-Brackmann Grade V facial palsy on the right side. After several hours, this improved to a Grade I. At the 1-month follow-up examination, the patient exhibited normal facial nerve function and stable hearing. Intracisternal papaverine may cause a transient facial nerve palsy by producing a temporary conduction block of the facial nerve. This adverse effect should be recognized when topical papaverine is used during CPA surgery.

Skeletonized Internal Thoracic Artery Harvest Reduces Pain and Dysesthesia and Improves Sternal Perfusion After Coronary Artery Bypass Surgery

Observational studies suggest that skeletonization of the internal thoracic artery (ITA) can improve conduit flow and length and reduce deep sternal infections and postoperative pain. We performed a randomized, double-blind, within-patient comparison of skeletonized and nonskeletonized ITAs in patients undergoing coronary surgery. Patients (n = 48) undergoing bilateral ITA harvest were randomized to receive 1 skeletonized and 1 nonskeletonized ITA. Intraoperatively, ITA flow was assessed directly and with a Doppler flow probe before and after topical application of papaverine. ITA harvest time and conduit length were recorded. A blinded assessment of pain (visual analog scale) and dysesthesia (physical examination) was performed at discharge, at 2 weeks, and at a 3-month follow-up. Sternal perfusion was assessed with nuclear imaging (n = 7). Skeletonization required longer ITA harvest times (27 +/- 1 versus 24 +/- 1 minutes; P = 0.04). There was a trend toward increased ITA length in the skeletonized group (18.2 +/- 0.3 versus 17.7 +/- 0.3 cm; P = 0.09). In situ ITA flow was lower in skeletonized arteries (7.4 +/- 0.9 versus 10.1 +/- 1.0 mL/min; P = 0.01) and increased significantly after ITA division and papaverine application. Postanastomotic flows were similar between groups. Skeletonization was associated with decreased pain at the 3-month follow-up and a reduction in major sensory deficits at the 4-week and 3-month (17% versus 50%; P = 0.002) follow-ups. Baseline adjusted sternal perfusion was significantly greater by 17 +/- 6% (P = 0.03) on the skeletonized side. Skeletonization results in reduced postoperative pain and dysesthesia and increased sternal perfusion at follow-up but does not produce increased conduit flow. ITA skeletonization may be a strategy for reducing morbidity after CABG.

Estimating oxygen consumption rates of arteriolar walls under physiological conditions in rat skeletal muscle

To examine the effects of vascular tone reduction on O2 consumption of the vascular wall, we determined the O2 consumption rates of arteriolar walls under normal conditions and during vasodilation induced by topical application of papaverine. A phosphorescence quenching technique was used to quantify intra- and perivascular PO2 in rat cremaster arterioles with different branching orders. Then, the measured radial PO2 gradients and a theoretical model were used to estimate the O2 consumption rates of the arteriolar walls. The vascular O2 consumption rates of functional arterioles were >100 times greater than those observed in in vitro experiments. The vascular O2 consumption rate was highest in first-order (1A) arterioles, which are located upstream, and sequentially decreased downstream in 2A and 3A arterioles under normal conditions. During papaverine-induced vasodilation, on the other hand, the O2 consumption rates of the vascular walls decreased to similar levels, suggesting that the high O2 consumption rates of 1A arterioles under normal conditions depend in part on the workload of the vascular smooth muscle. These results strongly support the hypothesis that arteriolar walls consume a significant amount of O2 compared with the surrounding tissue. Furthermore, the reduction of vascular tone of arteriolar walls may facilitate an efficient supply of O2 to the surrounding tissue.

Análise comparativa dos fluxos da artéria torácica interna esquerda dissecada na forma pediculada versus a forma esqueletizada em cirurgia de revascularização do miocárdio

To compare the free blood flow, caliber, and length of the left internal thoracic artery (LITA), dissected in the pedicled (P) and skeletonized (S) manners, during surgery before and after topical vasodilator (TV) application. A randomized, blind, clinical trial was carried out with 50 patients undergoing elective myocardial revascularization to assess the use of the LITA in situ in its pedicled or skeletonized form. The 25 patients in the pedicled group (GP) had NYHA class II or III angina, ejection fraction (EF) of 50.8+/-9.2%, and 16 were of the male sex. The patients in the skeletonized group (SG) had NYHA class II angina, EF of 46.8+/-9.3%, and 19 were of the male sex. The measurements were performed before extracorporeal circulation and divided into 2 phases: phase 1 (before topical papaverine application) and phase 2 (15 min after topical application of papaverine, 2.5 mg/mL, at 37 degrees C). During the measurements, mean blood pressure, central venous pressure, and heart rate were monitored. The phase 1 and 2 results are as follows: 1) PG: blood flow, 46+/-16 and 77+/-28 mL/min; caliber, 1.4+/-0.1 and 1.7+/-0.1 mm, respectively; 2) SG: blood flow, 57+/-27 and 97+/-35 mL/min; and caliber, 1.4+/-0.1 and 1.8+/-0.2 mm, respectively. No significant differences were observed in length. The LITA in SG had a significant increase in blood flow and caliber after the use of TV compared with blood flow and caliber in PG (P=0.03 and P=0.01, respectively).

Preventing internal auditory artery vasospasm using topical papaverine: an animal study.

Internal auditory artery (IAA) spasm is thought to be one of the causes of postoperative sensory hearing loss after attempted hearing preservation removal of an acoustic neuroma. The use of topical papaverine, a nonspecific vasodilator, to prevent vascular insufficiency to the inner ear and to improve hearing outcomes has been suggested but not proven. Vasospasm was mechanically induced by compressing the IAA in the control ears of six rabbits after application of topical saline. The subsequent reduction of cochlear blood flow (CBF) was measured using a laser-Doppler (LD) flow-monitoring technique. Functional loss of cochlear activity was verified with distortion product otoacoustic emissions (DPOAE). The contralateral experimental ears were treated with the topical application of papaverine directly to the IAA and cochleovestibular nerve complex. CBF and DPOAE were compared between the control and papaverine treated ears for 3-minute and 5-minute IAA compressions. Every control ear demonstrated some degree of postcompression IAA vasospasm (i.e., reduced CBF) and reduction of DPOAE. Nearly complete recovery of CBF and DPOAE to baseline was observed in all of the papaverine treated ears. An animal model of IAA vasospasm was described. Mechanically induced vasospasm of the IAA was prevented by the topical application of papaverine. These findings have clinical implications for surgical procedures involving the internal auditory canal/cerebellopontine angle such as acoustic neuroma removal.

Effect of Papaverine on Intraoperative BAEPs

ABSTRACT.Papaverine is a vasodilator agent that exerts a spasmolytic effect on smooth muscles, including cerebral blood vessels. We are not aware of reported cases of adverse effects of papaverine on evoked potentials. Two patients undergoing surgery for microvascular decompression to relieve hemifacial spasm exhibited transient changes on their brainstem auditory evoked potentials following the topical application of papaverine. Waves III and V could no longer be resolved after the application, while waves I and II persisted. Postoperatively, the BAEPs were present and the patients suffered no long term clinical sequelae related to the transient BAEP changes.

Skeletonized and pedicled internal thoracic artery grafts: Effect on free flow during bypass

The skeletonization technique of the internal thoracic artery (ITA) is used as a dissection technique for myocardial revascularization procedures. This study compared free flow between skeletonized ITA grafts and ITA pedicled grafts. The ITA pedicled grafts were sprayed and wrapped in sponges soaked in dilute papaverine solution in 14 patients and prepared with intraluminal papaverine injection in 18 patients. For 23 other patients, the ITA was skeletonized. We measured the first free flow from the distal ITA early after the start of cardiopulmonary bypass and the second free flow just before the ITA was grafted to the left anterior descending artery. The first flow was greater in the skeletonized ITAs than in the ITA pedicled grafts with topical application of papaverine alone (38.9 +/- 15.8 versus 18.0 +/- 6.8 mL/min; p < 0.001). For the second flow, the pedicle grafts with intraluminal papaverine injection and the skeletonized ITAs showed greater flow rate than the pedicled grafts with topical application of papaverine (67.4 +/- 25.5 and 59.7 +/- 22.5 versus 38.1 +/- 13.1 mL/min; p < 0.005 and p < 0.05, respectively), but there was no significant difference between the former two groups (p = 0.53). Skeletonization of the ITA is as efficient a strategy to increase the flow as intraluminal papaverine injection for the ITA pedicled graft. When the ITA is harvested in a skeletonized fashion, arterial spasm and reduced early flow can be avoided, even without intraluminal injection of papaverine.

Nitro-L-arginine attenuates hypercapnic cerebrovasodilation without affecting cerebral metabolism

We have previously demonstrated that topical cortical application of nitro-L-arginine (L-NA), a potent inhibitor of nitric oxide (NO) synthesis, attenuates resting cerebral blood flow (CBF) and the cerebrovasodilation elicited by hypercapnia. In this study, we sought to determine whether these cerebrovascular effects of L-NA are secondary to a depression in cerebral metabolism. Rats were anesthetized (chloralose, 80 mg/kg) and artificially ventilated. Arterial pressure and blood gases were monitored. The frontal cortex was exposed and superfused with normal Ringer (pH 7.3-7.4; 37 degrees C) or with Ringer containing L- or D-NA. CBF or cerebral glucose utilization (CGU) was measured autoradiographically using the [14C]iodoantipyrine or 2-[14C]deoxy-D-glucose method, respectively. Application of normal Ringer did not affect CBF at the site of superfusion (n = 5; P > 0.05, paired t test). Application of L-NA (1 mM; n = 5), but not D-NA (1 mM; n = 6), attenuated resting CBF by 33 +/- 5% (P < 0.05; analysis of variance). During hypercapnia (partial pressure of CO2 = 55-60 mmHg), L-NA attenuated the CBF increase by 78 +/- 6% (n = 5/group; P < 0.05 from Ringer), whereas D-NA had no effect (P > 0.05). Resting CBF and the CBF response to hypercapnia were largely unaffected in brain regions outside the field of superfusion. In contrast to hypercapnia, L-NA (1 mM) did not attenuate the increases in CBF elicited by topical application of papaverine (10-1,000 microM; n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of Wound Contraction by Papaverine: In Vitro Analysis with a Submucosal Tissue Model

We studied the effect of topical application of papaverine, a smooth-muscle relaxant, on the contraction of open, dorsal skin wounds in rats. Wound contraction was inhibited significantly in papaverine-applied wounds compared with saline-dressed control wounds. The in vitro effect of papaverine on wound contraction was studied by using human oral fibroblasts cultured three-dimensionally in the hydrated collagen gels containing papaverine. Papaverine inhibited collagen gel contraction in a dose-dependent manner. Any change in actin filament organization in fibroblasts cultured three-dimensionally in the collagen gels was observed by staining the filaments with fluorescent dye-conjugated phalloidin. In the control cultures, well-organized stress fibers were formed in the cell projections; in papaverine-treated fibroblasts, during the early stages of the treatment, the stress fibers were disrupted and actin filament aggregation was observed. In addition, papaverine induced a delay in the formation of the processes in fibroblasts cultured in collagen gels. These results indicate that wound contraction inhibition by papaverine is mediated by its effects on the organization of actin filaments of fibroblasts.

Effect of Serotonergic Antagonism on Local Responses to an Acute and Selective Endothelial Trauma in vivo

Serotonin is liberated during platelet release reaction. It is concluded from in vitro experiments that serotonin influences both platelet activation and thrombus-induced vasoconstriction. The subject of the present study was to assess the impact of the serotonin2 antagonist naftidrofuryl on both thrombogenesis and thrombus-induced vasoconstriction in vivo. In a hamster cheek pouch, vessels form a rich meshwork, allowing repetitive experiments to obtain intraindividual control measurements. With a contactless photochemical process, endothelial cells can be damaged in vivo. Regularly platelets and the coagulation system are activated and thrombi are formed. In larger arterial vessels local vasoconstriction occurs. Thrombogenesis was induced in arterioles with an inner diameter between 17 and 20 microns. It was monitored by the continuous measurement of blood cell velocity to assess initial hemodynamics and the interval elapsing until perfusion stops. Solvent alone had no effect. Naftidrofuryl was given in clinically relevant dosages of 1, 5, and 20 mg/kg intra-arterially. Even 1 mg/kg showed a significant antithrombotic effect. Efficacy increased in a dose-related manner as well as during the time interval of observation (i.e., 2 h after application). As an established antithrombotic standard, acetylsalicylic acid was applied in dosages of 10 and 100 mg/kg. Both dosages were found to be antithrombotic, but not more effective than comparable dosages of naftidrofuryl. Larger arterioles with an inner diameter of about 50 microns have smooth muscle cells. They constrict during thrombogenesis as a local response to substances released by the thrombus. Topical application of papaverine abolished vasoconstriction. A thromboxane antagonist (EP092) was also effective. Naftidrofuryl reduced the vasoconstriction whereas its solvent was without effect.

Deleterious effects of shock in internal mammary artery anastomoses

Internal mammary arteries (IMAs) are increasingly used for coronary artery revascularization. However, spastic reactions alter IMA-coronary artery anastomoses have been reported. Internal mammary artery flow and the effects of sudden hypovolemia, gradual hypovolemia, papaverine hydrochloride, nitrates, and epinephrine were evaluated in a canine model (n = 10) (body weight, 19 ± 5 kg) without interference from coronary artery resistance by dissecting the IMA as a pedicle, calibrating the flowmeter during free IMA flow, and anastomosing the IMA to the right atrium. Sudden hypovolemia (withdrawal of 20% of circulating blood volume over 90 seconds) caused significant modifications ( p < 0.01) of the following hemodynamic variables: heart rate (+12%), right atrial pressure (−17%), pulmonary artery pressure (−20%), wedge pressure (−30%), aortic pressure (−49%), cardiac output (−33%), distal IMA pressure (−54%), and IMA flow (−85%). During hypovolemia, IMA flow could not be increased with topical application of papaverine, but baseline values were achieved after retransfusion of the withdrawn blood volume. Gradual hypovolemia and application of large doses of nitrates showed less dramatic effects, and injection of an epinephrine bolus under rormovolemic conditions increased aortic pressure and IMA flow. Under sever hypovolemia, however, administration of an epinephrine bolus provoked only a minimal increase in aortic pressure and a contrasting decrease in IMA flow. We conclude that sudden, severe hypovolemia can lead to disproportionate IMA flow reduction and that pharmacological interventions are delicate under these circumstances.

Dose-related effects of adenosine and bradykinin on microvascular permselectivity to macromolecules in the hamster cheek pouch.

The hamster cheek pouch preparation was used to assess microvascular permselectivity responses to three vasodilating agents: bradykinin, adenosine, and papaverine. Fluorescein isothiocyanate-dextran 150 was injected intravenously as a macromolecular tracer. To quantify changes in permeability, we calculated fluorochrome clearance values from the ratio of suffusate to plasma fluorescein isothiocyanate-dextran 150 concentration. The microcirculation was recorded on videotape, using epifluorescence and bright-field light microscopy. Topical application of bradykinin elicited dose-dependent increases in macromolecular permeability. Adenosine also augmented permeability in a dose-dependent fashion. The increases in tracer clearance, relative to control, were 9.4 nl/min for 10(-5) M adenosine and 39.4 nl/min for 10(-4) M adenosine. The standard error for these doses was 1.5 nl/min. Adenosine, 10(-6) M, did not alter permeability. The increment in clearance induced by 10(-4) M was comparable to that of bradykinin, 8 X 10(-7) M. Pretreatment with phenidone had no effect on the permeability response mediated by 10(-5) M adenosine. Topical application of papaverine enhanced the transvascular exchange of macromolecules in one-half of the preparations examined. Comparable doses of adenosine were approximately three times as effective. This study indicated that adenosine, like bradykinin, is capable of modifying microvascular permeability responses in the hamster cheek pouch. This modulatory effect appears to be due to a direct action on the postcapillary microvascular membrane.

Blood flow reductions in stenosed canine coronary arteries: vasospasm or platelet aggregation?

In 67 dogs with a 60-80% coronary stenosis produced by an external constricting plastic ring, blood flow measured with an electromagnetic flowmeter showed cyclical flow reductions of varying magnitude and duration, and then an abrupt return to control flow. In 45 dogs, heparin did not prevent these flow reductions, but ibuprofen (Motrin) or indomethacin abolished them. With incremental doses of each of these drugs, the cyclical flow reduction and the platelet function in vitro were diminished proportionately. In 10 more dogs, during low flow, pinching or poking the narrowed vessel suddenly restored normal flow. Topical application of papaverine and nitroglycerin proximal to the stenosis did not abolish the cyclic flow reduction, although a transient fall in systemic pressure indicated that they had been absorbed. Seven dogs had the constricting cylinder and flow probe chronically implanted for 4-6 weeks. A single oral dose of aspirin, 20 mg/kg, abolished their cyclic flow reductions for 2-4 days. In five dogs with 70% stenosis in the circumflex coronary artery, coronary arteriography was performed before coronary flow reduction and when coronary blood flow was low. This showed that there was a considerable additional reduction in the size of the mechanically constricted lumen during spontaneous flow reduction. In one dog, a nonopacified mass was dislodged from the area of constriction in 67 msec and this restored the lumen to its control diameter. Similar rapid clearing was filmed in two more dogs. In no case was vasospasm observed. These results suggest that obstruction from platelets aggregated in the narrowed lumen caused the cyclic flow reductions.

Prevention of vasospasms during extensive renal surgery. An experimental study in rats.

Six methods for prevention of renal arterial vasospasms, due to extensive surgical trauma are compared in an experimental study in rats. The 'proximal transit time' was chosen as a measure for renal arterial flow 1, 5, 10 and 15 min after a standard surgical trauma. Xylocaine infiltration around the renal pedicle was least effective. Hydration of the rat, preoperative mannitol perfusion, and preoperative phenoxybenzamine treatment gave comparable effects and were significantly better than no treatment. The topical application of papaverine (1 mg/kg) around the renal pedicle did significantly better than the above-mentioned methods. The most effective treatment, however, was the combination of hydration, mannitol perfusion and papaverine application around the renal pedicle.

Morphological and physiological correlation of bradykinin-induced macromolecular efflux

Bradykinin applied topically for 4 min produced marked dose-related increases in the number of fluorescent dextran (mol wt 145,000) vascular leakage sites exclusively from small postcapillary venules--evidence for an increase in macromolecular permeability. The increase in macromolecular permeability was short-lived, making repeated applications possible. The number of bradykinin-induced venular fluorescent dextran leakage sites could be greatly reduced by the simultaneous topical application of isoproterenol, and this antagonism of the increase in macromolecular permeability could be prevented by pretreatment with propranolol. The topical application of papaverine failed to antagonize the increase in the number of venular leakage sites of fluorescent dextran by bradykinin. A continuous 90-min superfusion of bradykinin elicited an initial marked increase in the number of fluorescent dextran venular leakage sites, which then waned after 20-30 min, returning to near control despite the continued superfusion with bradykinin. In canine forelimbs the bradykinin-induced increase in protein efflux, total protein transport, and lymph flow also peaked in approximately 30 min and then waned markedly despite continued local intra-arterial infusions of this agent for prolonged periods. The morphological data from the cheek pouch agrees well with the physiological data from the forelimb, suggesting that an increase in protein efflux in the canine forelimb could be readily explained by an increase in the number of large pores.