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PubMed1987

Comparison of antihypertensive, renal hemodynamic, and humoral effects of pinacidil and hydralazine monotherapy.

The antihypertensive, renal hemodynamic, and humoral effects of pinacidil and hydralazine monotherapy were compared in a double-blind study. Supine diastolic blood pressure decreased with pinacidil (n = 14) from 96.5 to 82.6 mmHg (p less than 0.05), after a mean of 8.5 weeks at a mean dose of 64.3 mg/day, and with hydralazine (n = 15) from 101.5 to 94.0 mmHg (p less than 0.05), after 8.3 weeks at a dose of 163.3 mg/day. Renal plasma flow, glomerular filtration rate, and urinary albumin excretion did not change with pinacidil or hydralazine therapy. Neither agent altered plasma renin activity. Supine and upright plasma aldosterone concentrations decreased significantly during pinacidil, but not during hydralazine, therapy. Thus, both pinacidil and hydralazine reduced blood pressure and preserved renal function. During pinacidil therapy, plasma aldosterone concentrations decreased, whereas plasma renin activity did not. The mechanism of this response is unclear.

Adolescent↗

PubMed1987

Diuretic effect induced by intrarenal infusion of pinacidil in anesthetized dogs.

The diuretic action of pinacidil, a new vasodilating antihypertensive agent, was studied using anesthetized dogs. Intrarenally administered pinacidil (0.4, 2.0 and 10 micrograms/kg/min) produced a dose-related increase of renal blood flow, without altering mean arterial pressure. The glomerular filtration rate significantly increased only with the highest dosage. Pinacidil caused a dose-related augmentation of urine formation and, when given at 10 micrograms/kg/min, increased urine flow and urinary excretion of electrolytes to about 10 times and 3 to 9 times over the respective control value. In comparison, hydralazine (4.0 and 20 micrograms/kg/min) produced no significant diuretic action and bradykinin, given at a dose (0.02 micrograms/kg/min) equipotent to pinacidil (10 micrograms/kg/min) with respect to increasing renal blood flow, was less effective. Pinacidil administration significantly increased the fractional excretion of phosphate. Thus, pinacidil-induced diuresis seems to be due mainly to the vasodilating effect on renal vessels, with some contribution from an inhibitory effect on sodium reabsorption in the proximal tubules.

Anesthesia↗

PubMedDate not supplied

Relaxation of human uterine artery in response to pinacidil: predominant role for ATP-dependent potassium channels.

The effect of pinacidil on human isolated uterine artery rings was investigated. Pinacidil (10 nM-300 microM) induced a concentration-dependent relaxation of the precontracted arterial segments (pD2: 6.26; maximal response: 98.5%). Apamin (1 microM) and tetraethylammonium (6 mM) had no effects on the pinacidil-evoked relaxation, while 4-aminopyridine (0.1-6 mM) and glibenclamide (1-10 microM) competitively antagonized the response to pinacidil. The dissociation constants for 4-aminopyridine and glibenclamide were 240 microM and 0.40 microM, respectively. It is concluded that, in human uterine arteries, pinacidil induces relaxation. On the basis of differential antagonist affinities, we suggest that pinacidil produces a relaxation of this blood vessel through activation of glibenclamide-sensitive, ATP-dependent potassium channels.

4-Aminopyridine↗

PubMed1999

Effect of diltiazem and pinacidil on the response of the rabbit urinary bladder to repetitive stimulation and in vitro ischemia.

The effect of repetitive stimulation, in the presence and absence of diltiazem or pinacidil, on the contractile responses of isolated strips of rabbit bladder detrusor to field stimulation and carbachol, after 2 hr of incubation in a medium that serves as an in vitro model of ischemia (oxygen and substrate depleted Tyrode's solution), was determined. Our results are summarized as follows: a) The magnitude of the contractile dysfunctions after in vitro ischemia was enhanced by repetitive stimulation. b) Pre-incubation of isolated strips of detrusor with diltiazem (50 microM) inhibited the contractile responses to field stimulation (FS) and carbachol by 43 and 50%, respectively. Pinacidil (100 microM) inhibited the contractile responses to FS and carbachol by 37 and 32%, respectively. c) Neither diltiazem nor pinacidil protected the bladder strips against the effects of 2 hr of incubation in in vitro ischemia medium. However, d) both pinacidil and diltiazem reduced the level of contractile dysfunctions induced by repetitive stimulation. In conclusion, the contractile response to FS was significantly more sensitive to in vitro ischemia and repetitive stimulation than was the contractile response to carbachol. Both diltiazem and pinacidil protected the contractile responses to FS and carbachol from the degenerative effects of repetitive stimulation, but not from the effects of in vitro ischemia.

Animals↗

PubMed1990

Lack of effect of the vasodilator pinacidil on insulin secretion in healthy humans.

Pinacidil is a new antihypertensive vasodilator drug which is supposed to act by opening of ATP-sensitive and glibenclamide-sensitive K+ channels in vascular smooth muscle cell membranes. Similar K+ channels play an important role in insulin secretion from pancreatic islets cells. Inhibition of insulin secretion has been demonstrated with high concentrations of pinacidil in vitro. In the present study the insulin response to oral glucose were studied in six healthy subjects before and on the last day of 2 weeks treatment with pinacidil. The drug was given by the oral route 12.5 mg bid in the first week and 25 mg bid in the second. There were no significant changes in fasting blood levels of insulin or glucose, glucose-stimulated insulin secretion, or oral glucose tolerance during pinacidil administration. These results may suggest that pinacidil at therapeutic concentrations does not activate insulin regulating K+ channels in pancreatic islet cells.

Administration, Oral↗

PubMed1997

Pinacidil but not nicorandil opens ATP-sensitive K+ channels and protects against simulated ischemia in rabbit myocytes.

It has been proposed that ischemic preconditioning involves the regulation of ATP-sensitive potassium (K(ATP)) channels. The evidence is based largely on the ability of certain K(ATP) channel modulators to modify the protection in the various models of preconditioning. This study has investigated how two K(ATP) channel openers, pinacidil and nicorandil, affect both membrane currents and viability in isolated and ischemic rabbit cardiomyocytes. We used the whole-cell recording technique and in separate experiments viability was assessed by exposure to these drugs during ischemia. Pinacidil (50 micromol/l) increased K(ATP) current approximately four-fold in isolated cardiomyocytes. This increase reversed rapidly after treatment with the K(ATP) channel blocker glibenclamide (200 nmol/l). After simulated ischemia, pinacidil protected cardiomyocytes (the area under cell-death curve was 29.5 +/- 1.1% x h) which was significantly less than that in control (46.9 +/- 2.0% x h). The protection from pinacidil could be completely eliminated by pretreatment with 10 microM glibenclamide (46.9 +/- 2.0% x h). In contrast, nicorandil (1 mmol/l), which opens K(ATP) channels in some tissues, caused no detectable effect on the K(ATP) current. Similarly, nicorandil did not produce cardioprotection. These results indicate that pinacidil and nicorandil have very different effects on rabbit cardiomyocyte K(ATP) channels. Furthermore, because protection correlated with the ability of the agent to open the channel, they support a role for K(ATP) channels in preconditioning.

Adenosine Triphosphate↗

PubMed2000

Pinacidil pretreatment extends ischemia tolerance of neonatal rabbit hearts.

OBJECTIVES: Activating ATP-sensitive potassium (K(ATP)) channels improves ischemia tolerance of adult rabbit hearts. We hypothesize that (a) endogenous activation of the K(ATP) channel accounts for better ischemia tolerance of neonatal hearts and (b) exogenous K(ATP) channel activation with pinacidil further improves the neonatal heart's tolerance to cardioplegic ischemia. METHODS: Study 1: Seven (control) neonatal rabbits received intraperitoneal saline, whereas five others (Glib) received 0.3 mg/kg glibenclamide 10 min before sacrifice. They were perfused on Langendorff with Krebs-Henseleit buffer (KHB). Baseline left ventricle (LV) performance and coronary flow (CF) were measured. After 20 min of 37 degrees C ischemia and 10 min of reperfusion, recovery was measured. Study 2: Ten (control) neonatal hearts underwent 90 min of normothermic ischemia with St. Thomas' cardioplegia (STCP) solution administered every 30 min. Ten others were pretreated with a 10-min infusion of 1 microM pinacidil in KHB and received 1 microM pinacidil-enriched STCP. Recovery of LV performance and CF were measured after 60 min of reperfusion. RESULTS: Study 1: Glib significantly reduced preischemia LV performance by 28%* compared to control hearts. Recovery of Glib-treated hearts was significantly less (67%*) than controls (81%*). Study 2: Pinacidil-treated hearts had significantly better recovery of LV performance (39%*) and CF (78%*) compared to 23 and 52%, respectively, in untreated controls (*P < 0.05 vs control hearts). CONCLUSIONS: Endogenous K(ATP) channel activation in neonatal hearts contributes to their better tolerance to ischemia. Exogenous K(ATP) channel activation by pinacidil pretreatment and cardioplegic enrichment significantly improved the neonatal rabbit heart's tolerance to cardioplegic ischemia. This may be an important addition to myocardial protection during pediatric cardiac surgery.

Animals↗

PubMed1993

Relaxant effects of the potassium channel activators BRL 38227 and pinacidil on guinea-pig and human airway smooth muscle, and blockade of their effects by glibenclamide and BRL 31660.

The airways relaxant effects and mechanism of action of the potassium channel activators BRL 38227 and pinacidil have been compared in guinea-pig and human airways. BRL 38227 was a potent relaxant in guinea-pig isolated trachealis (IC50 = 4.9 x 10(-7) M against spontaneous tone) and human isolated bronchi (IC50 = 4.75 x 10(-7) M against histamine-induced tone) and was eight- and six-fold more potent respectively than pinacidil. The relaxant effects of both compounds were shown to be markedly attenuated by glibenclamide (10(-5) M) and BRL 31660 (10(-5) M), with the nature of the blockade being species/tissue dependent. Glibenclamide (20 mg/kg iv) also inhibited the protective effects of BRL 38227 (50 micrograms/kg iv) and pinacidil (500 micrograms/kg iv) on histamine-induced changes in airways resistance and dynamic compliance in the anaesthetized guinea-pig, although the effects were short-lived. That both BRL 38227 and pinacidil owed their relaxant effects to potassium channel activation was supported by their ability to stimulate 42/43K efflux from guinea-pig trachealis preloaded with the radiotracer at concentrations of 10(-7) - 10(-5) M and 10(-5) M respectively. Pretreatment with either glibenclamide (10(-5) M) or BRL 31660 (10(-5) M) ablated the response to both compounds. These studies show that two mechanistically distinct potassium channel blockers, glibenclamide and BRL 31660, do not substantially differentiate between the actions of BRL 38227 and pinacidil, although differences do occur, particularly at high concentrations in vitro.

Animals↗

PubMed1993

Effects of pinacidil on cerebral and mesenteric arteries--influence of the endothelium.

The effect of pinacidil on the contractile response to stepwise increases of the extracellular K+ concentration ([K+]o) was investigated in isolated segments of human pial and mesenteric arteries and rabbit basilar and mesenteric arteries. The [K+]o eliciting half maximum contraction (EC50) was lower in human pial (18 mM) and rabbit basilar (27 mM) arteries than in human (33 mM) and rabbit (32 mM) mesenteric arteries, respectively. The alpha-adrenoceptor blocker, prazosin, increased the EC50 value for K+ from 27 to 40 mM and reduced the maximum response in rabbit mesenteric arteries, but had no effect on the K(+)-induced contraction in rabbit basilar arteries, indicating a substantial noradrenergic component of the K+ response in the former arteries. Removal of the endothelium decreased the EC50 value for K+ from 27 to 15 mM in rabbit basilar arteries, whereas the K+ sensitivity was unaffected in rabbit mesenteric arteries. Pinacidil shifted the K+ concentration-response curve to the right in human and rabbit cerebral and mesenteric arteries. In rabbit basilar arteries, but not in mesenteric arteries, the shift was larger in the absence than in the presence of an intact endothelium. When endothelium-denuded rabbit arteries were compared, the inhibitory effect of pinacidil was larger in basilar than in mesenteric arteries. Thus, pinacidil inhibits K(+)-induced contractions in both cerebral and mesenteric arteries, but appears to act preferentially on endothelium-denuded rabbit basilar arteries. Provided that endothelial damage and depolarization-induced vasoconstriction are of pathophysiological importance in cerebrovascular disorders such as stroke and cerebral ischemia secondary to vasospasm after subarachnoid hemorrhage, pinacidil may have a therapeutic potential.

Adrenergic alpha-Antagonists↗

PubMed1991

Differential antagonism by glibenclamide of the relaxant effects of cromakalim, pinacidil and nicorandil on canine large coronary arteries.

The relaxant mechanisms of action of cromakalim, pinacidil and nicorandil, potassium channel openers, on large epicardial coronary arteries were investigated in isolated canine left circumflex arteries contracted by 10(-7) mol/l U46619, a thromboxane A2 analogue, or addition of 25 mmol/l KCl in comparison with nitroglycerin. Cromakalim (3 x 10(-8)-3 x 10(-5) mol/l), pinacidil (10(-6)-10(-4) mol/l), nicorandil (3 x 10(-6)-10(-3) mol/l) and nitroglycerin (3 x 10(-8)-10(-5) mol/l) all produced a concentration-dependent relaxation in both U46619- or KCl-contracted arteries. At their maximum effects pinacidil, nicorandil and nitroglycerin produced full relaxation in arteries contracted by either means. In contrast, cromakalim produced about a 73% relaxation in KCl-contracted arteries, although it caused full relaxation in U46619-contracted ones. In the presence of glibenclamide the concentration-relaxation curves for cromakalim in U46619- or KCl-contracted arteries underwent rightward parallel shifts. Schild regression had a slope of 1.00 and yielded a pA2 of 7.47 for glibenclamide in U46619-contracted arteries, and corresponding values obtained in KCl-contracted arteries were 0.86 (not significantly different from unity) and 7.28. The concentration-relaxation curves for pinacidil in U46619-contracted arteries also underwent rightward parallel shifts in the presence of glibenclamide, however, Schild regression had a slope of 0.60. The concentration-relaxation curves for pinacidil in KCl-contracted arteries underwent rightward parallel shifts only to a limited extent in the presence of glibenclamide. The concentration-relaxation curves for nicorandil and nitroglycerin in U46619- or KCl-contracted arteries were not affected by glibenclamide in concentrations which antagonized cromakalim.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1987

Chronic effects of direct vasodilation (pinacidil), alpha-adrenergic blockade (prazosin) and angiotensin-converting enzyme inhibition (captopril) in systemic hypertension.

Chronic responses of systemic hemodynamics and blood pressure counterregulatory ("pseudo-tolerance") mechanisms were investigated in matched groups of patients with essential hypertension after 1 month of vasodilator therapy with pinacidil (a direct arterial dilator), prazosin (an alpha 1-adrenergic blocking drug) or captopril (an angiotensin-converting enzyme inhibitor). For equivalent decreases in mean arterial pressure compared with placebo baseline (approximately 8 mm Hg supine and 12 mm Hg upright), prazosin and captopril did not increase cardiac index or heart rate. In contrast, marked decreases in systemic vascular resistance with pinacidil (approximately 25%, p less than 0.05) were accompanied by reflex increases in cardiac index (approximately 20%, p less than 0.05). Activity of the sympathetic nervous system, measured by supine and upright plasma norepinephrine (NE), increased approximately 50% with pinacidil and prazosin (p less than 0.001 each), whereas captopril decreased supine plasma NE by 12% (p less than 0.05) and did not change upright plasma NE. All 3 drugs caused an expansion of height-adjusted blood volume (approximately 14%). Pinacidil and prazosin caused reversible weight gains of 0.9 and 0.7 kg, respectively, whereas captopril reversibly decreased body weight by 0.8 kg (p less than 0.05), suggesting differential effects of the 3 drugs on interstitial fluid volume. During chronic therapy, all 3 drugs may require concomitant diuretic therapy, whereas concomitant sympatholytic therapy may be required with the potent vasodilator pinacidil. Captopril may be associated with the lowest cardiac risk because of its lack of stimulatory effects on the sympathetic nervous system and cardiac index.

Adrenergic alpha-Antagonists↗

PubMed1994

Effect of pinacidil on rat hearts undergoing hypothermic cardioplegia.

We studied the effect of pinacidil, a potassium-channel opener, on the hemodynamic, biochemical, and ultrastructural changes in rat hearts undergoing hypothermic cardioplegia. Fifty-four male Wistar rats weighing 250 to 300 g were used. Isolated hearts were prepared for modified Langendorff circulation in the working mode using modified Krebs-Henseleit bicarbonate solution bubbled with a 95% O2 and 5% CO2 gas mixture. Eighty minutes of cardioplegia at 25 degrees C was followed by normothermic reperfusion for 30 minutes. Pinacidil, 5, 10, or 50 mumol/L added to the cardioplegic solution, did not affect heart rate, but is significantly improved the recovery of aortic flow as compared with controls (88.1% +/- 4.3 [5 mumol/L]; 83.2% +/- 8.5% [10 mumol/L]; 90.3% +/- 5.3% [50 mumol/L] compared with 55.6 +/- 4.3% [control]; p < 0.05). Administration of pinacidil during reperfusion did not further enhance the recovery of aortic flow. The dose-response curve of aortic flow to the pinacidil concentrations was flat from 5 to 50 mumol/L. However, preservation of myocardial adenosine triphosphate and calcium concentrations and mitochondrial morphology suggested that the optimal concentration of pinacidil cardioplegia is 10 mumol/L.

Animals↗

PubMed1996

Myocardial protection with pinacidil cardioplegia in the blood-perfused heart.

BACKGROUND: Adenosine triphosphate-sensitive potassium-channel openers are potent vasodilators that have been found to be cardioprotective during myocardial ischemia. The potassium-channel opener pinacidil was investigated to determine its efficacy as a cardioplegic agent. METHODS: A blood-perfused, parabiotic, isolated rabbit heart Langendorff preparation was used. Fifty-six hearts underwent 30 minutes of global normothermic ischemia after a 50-mL infusion of cardioplegia, followed by 60 minutes of reperfusion. The cardioplegia consisted of Krebs-Henseleit solution with either vehicle alone (control), 20 mmol KCl, or pinacidil (10, 50, 100, 150, or 200 mumol/L). The developed pressure was measured at baseline and after reperfusion. Coronary blood flow was measured with an in-line ultrasonic probe. RESULTS: Pinacidil (50 mumol/L), as opposed to potassium cardioplegia, provided significantly better postischemic percentage recovery of developed pressure compared with controls (68.3% +/- 4.0% versus 44.6% +/- 5.5%; p < 0.05). The time until electrical arrest was significantly shorter in the hyperkalemic group than in all other groups. Linear end-diastolic pressure-volume relationships revealed an increase in slope after ischemia in all groups. Coronary flow after 5 minutes of reperfusion was significantly higher in both the 50-mumol/L and 100-mumol/L pinacidil groups compared with traditional hyperkalemic arrest, and this returned to baseline after 15 minutes. CONCLUSIONS: The potassium channel opener pinacidil provided dose-dependent myocardial protection during global ischemia in the blood-perfused rabbit heart model. Potassium-channel openers are a promising class of drugs that may provide an alternative to traditional hyperkalemic cardioplegia.

Animals↗

PubMed1989

Haemodynamic differences between cromakalim and pinacidil: comparison with nifedipine.

The effects of cromakalim (0.015, 0.03 and 0.06 mg kg-1 p.o.), pinacidil (0.3, 0.6 and 1.2 mg kg-1 p.o.) and nifedipine (0.15, 0.3 and 0.6 mg kg-1 p.o.) were compared on mean arterial pressure (MAP), heart rate (HR), mean renal blood flow (MRBF) and plasma renin activity (PRA) in the conscious normotensive cat. All drugs elicited dose-related falls in MAP with cromakalim being about 10 times more potent than nifedipine or pinacidil, the latter two drugs being equipotent. For similar reductions in MAP, the increases in HR and PRA produced by cromakalim were significantly smaller than those produced by either nifedipine or pinacidil. Cromakalim (0.015-0.06 mg kg-1 p.o) elicited dose-related increases in MRBF with the peak effect occurring 2-2.5 h post-dose. Thereafter, MRBF recovered toward pretreatment levels despite MAP being almost maximally reduced. Neither nifedipine nor pinacidil affected MRBF though nifedipine (0.3 mg/kg-1 p.o.) caused a significant reduction in renal vascular resistance. This study has shown that important haemodynamic differences exist between cromakalim, nifedipine and pinacidil suggesting that increased MRBF is not a general property of K+ channel activation or of Ca2+ slow channel blockade.

Animals↗

PubMed1989

A comparison of the relaxant effects of pinacidil in guinea-pig trachea, aorta and pulmonary artery.

The relaxant activity of pinacidil, a proposed K+ channel opener, was compared in isolated guinea-pig trachea, aorta and pulmonary artery. In preparations precontracted by histamine or PGF2 alpha, pinacidil produced complete tracheal relaxation but only partial relaxation of vascular tissues. The order of responsiveness was: pulmonary artery greater than trachea greater than aorta. The slope of the pinacidil concentration-effect (C/E) curve was much steeper in the tracheal than in the vascular preparations. The pinacidil C/E curves for relaxation were similar when the three types of preparations were precontracted by 124 mM K+. Pretreatment with pinacidil caused a parallel shift of the tracheal histamine C/E curve to the right, whereas the maximal response to histamine was markedly depressed in the pulmonary artery.

Animals↗

PubMed1990

Glibenclamide blocks the relaxant action of pinacidil and cromakalim in airway smooth muscle.

Concentration-relaxation curves for pinacidil and cromakalim were obtained in isolated guinea-pig tracheas contracted by histamine. Pinacidil produced complete relaxation with an EC50 value of 2.8 microM. The antidiabetic sulfonylurea, glibenclamide (0.1, 1, 10 microM), caused concentration-dependent rightward shifts (3- to 16-fold) of the concentration-relaxation curve for pinacidil without changing the maximal relaxant response. Cromakalim produced 85% relaxation with an EC50 value of 1.1 microM. Glibenclamide (0.1 microM) displaced the concentration-relaxation curve to the right and at higher concentrations (1-10 microM) caused nearly complete suppression of the maximal relaxant response to cromakalim. Glibenclamide not only prevented the effects of pinacidil and cromakalim but also produced a concentration-dependent and complete reversal of submaximal relaxations produced by these drugs. Glibenclamide was a selective antagonist of the relaxation of airway smooth muscle induced by pinacidil and cromakalim. Concentration-relaxation curves for theophylline, terbutaline and verapamil were unaffected by glibenclamide.

Animals↗

PubMed1991

Effects of pinacidil and other cyanoguanidine derivatives on guinea-pig isolated trachea, aorta and pulmonary artery.

The effects of pinacidil and four other cyanoguanidine derivatives (P 1060, P 1106, P 1787, P 1890) were evaluated on guinea-pig isolated trachea, aorta and pulmonary artery. All compounds were effective smooth muscle relaxants. Concentration-relaxation curves and corresponding EC50 and Emax values were determined in preparations contracted by histamine, prostaglandin F2 alpha, 30 mM K+ or 124 mM K+. Pinacidil relaxed trachea by 100% and vascular tissues by 70%. P 1060 and P 1106 also produced complete tracheal relaxation, but had a lower maximal effect of 40% in vascular smooth muscle. P 1787 and P 1890 relaxed all three types of tissues by 100%. The order of potency of the drugs was P 1106 greater than P 1060 greater than pinacidil greater than P 1890 greater than P 1787. Pinacidil, P 1060 and P 1106 were more potent on pulmonary artery than on aortic preparations. Based on the effects of the drugs on 30 mM K(+)- and 124 mM K(+)-induced contractions and the ability of glibenclamide to antagonize the drugs, P 1060 and P 1106 appeared to be pure K+ channel openers whereas pinacidil seemed to operate by additional mechanisms. P 1787 and P 1890 relaxed smooth muscle by a mechanism other than opening of K+ channels.

Animals↗

PubMed2003

Warm ischemia lung protection with pinacidil: an ATP regulated potassium channel opener.

BACKGROUND: Ischemia/reperfusion injury remains a limiting factor in lung transplantation. Traditional hyperkalemic preservation solutions are associated with a host of metabolic derangements. ATP-regulated potassium channel openers (PCOs) may provide an attractive alternative to traditional solutions by utilizing inherent mechanisms of ischemic preconditioning. The purpose of this study was to assess warm ischemia graft protection with pinacidil, a nonspecific PCO. METHODS: An isolated recirculating blood perfused ventilated rabbit lung model was used (n = 15). No ischemia control lungs underwent immediate reperfusion (n = 5). Warm ischemia control lungs were flushed with lactated Ringers (LR), stored at 37 degrees C for 2.5 hours and then reperfused for 2 hours (n = 5). PCO protected lungs were flushed with LR + 100 micromol/L pinacidil, stored, and then reperfused (n = 5). Intermittent blood gases were taken from the pulmonary artery and left atria. Every 30 minutes, graft function was assessed with a 10-minute 100% fractional inspired oxygen concentration challenge to measure maximal gas exchange. Lung samples were graded for histologic injury and assayed for myeloperoxidase activity. RESULTS: A mixed-models repeated measures ANOVA demonstrated a significant difference between groups. Tukey's honestly significant difference multiple comparison test demonstrated significantly improved graft function and reduced histologic injury with pinacidil protection compared with the warm ischemia controls. There was no significant difference in graft function or pathology grade between the pinacidil protected lungs and the no ischemia controls. A similar trend, although not significant, was seen in myeloperoxdiase activity. CONCLUSIONS: Potassium channel openers with pinacidil can provide pulmonary protection against warm ischemia reperfusion injury.

Animals↗