Intravenous Pluronic F-127 in early burn wound treatment in rats.

A dramatic improvement in full skin thickness burn wounds in rats treated intravenously with the non-ionic surfactant Pluronic F-127 (F-127) has been demonstrated. In this study the F-127 was given 30 min postburn to simulate conditions encountered in a clinical setting. Anaesthetized male rats (300-320 g) received full skin thickness burns by immersion of the anterior chest wall (8 per cent body surface area in a 70 degrees C water-bath for 12 s). Burn wound area was measured immediately and after 48 h. Thirty minutes after the burn, half the animals received equal volumes (8 ml/kg body wt) of either saline or F-127 (12 mM/l concentration) via the tail vein. The animals autopsied at 48 h showed a significant (P < 0.05) reduction in the degree of wound contraction and the wound appeared grossly less damaged in the F-127-treated animals. Histologically, skin biopsies showed less of the microscopic damage usually associated with full skin thickness burns in the F-127-treated animals than in the saline controls. We also used thermography to measure skin temperature of the burn area at 90 min and 48 h postinjury demonstrating alterations in the F-127-treated animals (P < 0.05). In animals followed for 30 days postinjury, there was a significant (P < 0.01) improvement in the wound closure rates in the F-127-treated animals. These observations show a positive therapeutic effect of F-127 on the inflammatory process in the area of a burn that may improve wound healing.

Comparative effects of PGD2 and PGE2 in the regional circulation of the cat.

The peripheral vascular effects of PGD2 and PGE2 were investigated in the anesthetized cat. PGD2 and PGE2 caused dose-related decreases in hindquarters and renal perfusion pressure whereas intestinal responses to these substances were divergent. Since regional blood flows were held constant with a pump, changes in perfusion pressure directly reflect changes in hindquarters, renal and intestinal vascular resistance. PGD2 and PGE2 had similar vasodilator activity in the hindquarters vascular bed. In the renal vascular bed, the dilator response to high doses of PGD2 was greater than to PGE2 whereas the low dose of PGE2 produced a greater reduction in renal vascular resistance. In the intestinal vascular bed, bolus injections and infusion of PGE2 decreased vascular resistance whereas PGD2 had biphasic effects possessing an initial vasoconstrictor component. These data demonstrate that PGD2 and PGE2 have significantly vasoactivity in the regional circulation. In addition, the relative vasodilator effects of PGE2 are organ dependent and the effects of PGD2 depend on both organ and dose in the cat.

Blockade of vasoconstrictor responses by prostacyclin (PGI2), PGE2, and PGE1 in the rabbit hindquarters vascular bed.

The effects of infusions of prostacyclin (PGI2), PGE2 and PGE1 on responses to pressor hormones and sympathetic nerve stimulation were investigated in the hindquarters vascular bed of the rabbit. During infusions of PGI2, PGE2 and PGE1 vasoconstrictor responses to norepinephrine, nerve stimulation and angiotensin II were decreased. Responses to the pressor hormones and nerve stimulation were decreased to a similar extent by PGI2 and responses returned to control value 30 min after the infusion. During infusions of PGE2 and PGE1 responses to nerve stimulation were decreased to a somewhat greater extent than responses to pressor hormones and the inhibitory action of these substances had a longer duration of action than PGI2. Indomethacin in doses that blocked depressor responses to arachidonic acid was without consistent effect on responses to nerve stimulation and pressor hormones. The present data show that E series prostaglandins and PGI2 possess the ability to modulate responses to nerve stimulation and pressor hormones; however, experiments with indomethacin suggest that endogenous prostaglandins do not modulate vasoconstrictor responses in the rabbit hindquarters.

Cardiovascular actions of prostacyclin (PGI2) in the cat.

The cardiovascular actions of the newly discovered bicyclic prostaglandin, prostacyclin, or PGI2, were compared with those of PGE1 in the anesthetized cat. PGI2 decreased systemic arterial pressure, increased cardiac output and decreased systemic vascular resistance. The decreases in systemic vascular resistance were similar when PGI2 was injected into the left or right atrium, suggesting that prostacyclin is not inactivated in the feline pulmonary vascular bed. PGE1 also decreased systemic arterial pressure and increased cardiac output; however, left atrial administration of this substance produced greater reductions in systemic vascular resistance than right atrial injections, suggesting that PGE1 is inactivated in the feline lung. PGI2 also caused dose-related decreases in perfusion pressure in the renal, hindquarters and mesenteric vascular beds and had the greatest vasodilator activity in the mesenteric vascular bed. PGE1 decreased perfusion pressure in the 3 regional beds, and the overall dilator effects of PGI2 and PGE1 in the peripheral circulation were quite smiliar. The present data show that PGI2 is a potent peripheral vasodilator in the cat and since this substance is not inactivated in the lung, it could serve as a circulating hormone in this species.

Influence of prostaglandin E2, indomethacin, and reserpine on renal vascular responses to nerve stimulation, pressor and depressor hormones.

The effects of prostaglandin E2 (PGE2) indomethacin, and reserpine were evaluated in the rabbit renal vascular bed in situ under conditions of controlled blood flow. Intrarenal infusion of PGE2, 0.03 and 0.3 microgram/min, decreased responses to renal nerve stimulation, intra-arterial norepinephrine, and angiotensin. Responses to nerve stimulation were decreased to a greater extent than responses to norepinephrine. At lower concentrations the effects of PGE2 on pressor responses and on vascular resistance could be separated. Reserpine decreased the histochemical evidence of adrenergic innervation and reduced the response to renal nerve stimulation, enhanced the response to norepinephrine, and was without effect on the response to angiotensin. Indomethacin decreased depressor responses to arachidonic acid, produced a small increase in renal vascular resistance but did not enhance renal pressor responses. The increase in renal vascular resistance after indomethacin was not modified by reserpine pretreatment. Indomethacin enhanced the renal response to bradykinin. These data show that PGE2 possesses the ability to modulate pressor responses in the kidney. However, experiments with indomethacin suggest that endogenous prostaglandins neither modulate pressor responses nor mediate the response of the renal vascular bed to bradykinin. In addition, these data suggest that the increase in renal resistance after indomethacin is not dependent on the adrenergic nervous system.

Influence of inhibitors of prostaglandin synthesis on renal vascular resistance and on renal vascular responses to vasopressor and vasodilator agents in the cat.

We determined the effects of indomethacin and meclofenamate, two inhibitors of prostaglandin synthesis, on renal vascular resistance and on renal responses to nerve stimulation, pressor and depressor hormones in the in situ feline kidney under conditions of controlled blood flow. Both inhibitors produced a gradual rise in renal vascular resistance which became maximal 15-20 minutes after administration. The increase in renal resistance after indomethacin was not attenuated during intrarenal infusion of either phentolamine or SQ 20881. Pretreatment with propranolol, in a dose sufficient to inhibit renin secretion, also did not attenuate the increase in renal resistance produced by indomethacin. However, infusion of [Sar1-, Ala8]angiotensin II, an angiotensin II antagonist, did attenuate the indomethacin-induced increase in renal vascular resistance. After indomethacin, the vasoconstrictor response to norepinephrine was enhanced, whereas responses to nerve stimulation and angiotensin were unaffected. Although meclofenamate enhanced renal vascular resistance, its effects on vasoconstrictor responses were inconsistent. After indomethacin, the renal dilator response to bradykinin was enhanced; however, dilator responses to nitroglycerin were unaltered. The present data indicate that the increase in renal vascular resistance after indomethacin does not depend on the adrenergic system but may be dependent on the renin-angiotensin system. The inconsistent effect of the inhibitors of synthesis on renal constrictor responses to nerve stimulation suggests that endogenous prostaglandins do not serve to modulate the effects of the sympathetic nervous system on the feline renal vascular bed. These results also indicate that renal dilator responses to bradykninin are not mediated by prostaglandins in the cat.

Effects of 13, 14-dehydroprostacyclin methyl ester on the feline intestinal vascular bed.

The effects of a stable PGI2 analog, 13, 14-dehydro-PGI2 methyl ester and several vasoactive hormones were compared in the feline intestinal vascular bed under conditions of controlled blood flow so that changes in perfusion pressure directly reflect changes in vascular resistance. The PGI2 analog decreased perfusion pressure in a dose-dependent fashion when injected in the range of dose of 0.03-3 microgram and was quite similar to PGE2 whereas isoproterenol was somewhat more potent as a vasodilagor in the feline intestinal vascular bed. The present data show that 13, 14-dehydro-PGI2 methyl ester has potent vasodilator activity in the intestinal vascular bed.

Influence of prostaglandins E, A and F on vasoconstrictor responses to norepinephrine, renal nerve stimulation and angiotensin in the feline kidney.

The effects of intrarenal infusion of prostaglandins (PGs) of the E, A and F series on renal vascular resistance and on vasoconstrictor responses to renal nerve stimulation (RNS), norepinephrine (NE) and angiotensin (A) were determined in the in situ feline kidney under conditions of controlled blood flow. Infusion of PGE2 (3 and 0.3 mug/min) and PGE1 (3 mug/min) resulted in a marked decrease in renal perfusion pressure and a reduction in responses to all vasoconstrictor stimuli. PGE2 (0.03 mug/min) did not alter perfusion pressure. However, responses to RNS and A but not to NE were attenuated. PGA2 (3 and 0.3 mug/min) had no significant effect on perfusion pressure. PGA1 (3 mug/min) resulted in a transient decrease in renal vascular resistance which was not maintained during the infusion period. PGA2 (3 mug/min) reduced the response to RNS at 10 and 30 cps and reduced the response to A, whereas responses to NE were not affected. PGA2 (0.3 mug/min) had no effect on responses to either of the pressor stimuli. PGA1 infusion resulted in an enhanced response to RNS at the highest stimulus frequency and decreased the response elicited by A. PGF2alpha (3 mug/min) had no significant effect on renal vascular resistance or on responses to NE and nerve stimulation. However, the response to angiotensin was decreased and responses to RNS at 10 and 30 cps were decreased 30 minutes after the PGF2alpha infusion. The present data demonstrate that, of the natural renal PGs, PGE2 and PGA2 possess the capacity to modulate the effects of the sympathetic nervous system on the feline kidney. In addition, the effects of PGE and PGA on responses to adrenergic stimuli and on vascular resistance could be separated.