Effect of ACTH-(1-24) on the volume of circulating blood and on regional blood flow in rats bled to hypovolemic shock

Influence of ACTH‐(1–24) on free radical levels in the blood of haemorrhage‐shocked rats: direct ex vivo detection by electron spin resonance spectrometry

“…This effect of ACTH-(1-24) is prompt (reaching its maximum 15 min after treatment) and long-lasting (the free radical blood level remains quite stable throughout the 2 h observation period). It parallels the effects of ACTH-(1-24) on arterial pressure and tissue blood flow (Bertolini et al, 1989;Guarini et al, 1989). This effect cannot be attributed to an ACTH-(1-24) radical scavenging activity, as demonstrated by the competition experiment.…”

Influence of ACTH‐(1–24) on free radical levels in the blood of haemorrhage‐shocked rats: direct ex vivo detection by electron spin resonance spectrometry

“…This effect of ACTH-(1-24) is prompt (reaching its maximum 15 min after treatment) and long-lasting (the free radical blood level remains quite stable throughout the 2 h observation period). It parallels the effects of ACTH-(1-24) on arterial pressure and tissue blood flow (Bertolini et al, 1989;Guarini et al, 1989). This effect cannot be attributed to an ACTH-(1-24) radical scavenging activity, as demonstrated by the competition experiment.…”

Melanocortins and the Cholinergic Anti-Inflammatory Pathway

“…Such increase is the consequence of mobilization of the peripherally pooled residual blood from the liver, spleen and other organs. 28,83,85 Subsequent studies using the same experimental model indicated that melanocortins greatly prolong survival and extend the time-limit for effective blood reinfusion (up to 3-4 hours after shock, versus 10-15 min in saline-treated animals) for complete shock reversal. 29 These resuscitating effects have been confirmed in the same animal models of hemorrhagic shock, 86 as well as in hemorrhage-shocked/resuscitated hamsters, 87 in hypovolemic shock induced in rabbits by graded occlusion of the inferior vena cava, 88 in a rat model of splanchnic artery occlusion 34 and in a severe model of prolonged respiratory arrest in rats.…”

“…This procedure causes death in all animals within 30-35 min. 26,27,[81][82][83] Conversely, intravenous injection of melanocortin peptides rapidly induces a dose-dependent restoration of arterial blood pressure and tissue blood flow. Normalization of arterial and venous pH and base excess, as well as of venous tension of O 2 and CO 2 and of venous oxygen saturation and lactate, also gradually occur.…”

Resuscitating effect of melanocortin peptides after prolonged respiratory arrest

“…injection of mela‐nocortin peptides (adrenocorticotrophin (ACTH), α‐melanocyte stimulating hormone (α‐MSH), other ACTH fragments: 1–24, 1–18, 1–17, 1–16, 4–10) in nanomolar amounts, dose‐dependently restores arterial pressure, pulse amplitude and respiratory function, and produces a highly significant prolongation of the survival time (Bertolini et al , 1986a,b,c, 1989; Guarini et al , 1990; Bertolini, 1995). This effect is adrenal‐independent (it is obtained also in adrenalectomized animals, and with melanocortin peptides practically devoid of corticotropic activity) (Bertolini et al , 1986a,c), and is associated with a massive increase in the volume of circulating blood, with consequent restoration of the blood flow (Guarini et al , 1987; 1989), normalization of cardiac output and total peripheral resistances, gradual normalization of arterial and venous pH and base excess (BE), as well as of venous tension of O 2 ( P O 2 ) and CO 2 ( P CO 2 ) and venous oxygen saturation (Hb/O 2 ) and lactate (Bazzani et al , 1992), and with greatly reduced free radical levels in blood (Guarini et al , 1996). Although these peptides do not per se definitively cure haemorrhagic shock (all rats treated with the maximally active dose of 160 μg kg −1 die within 44 ± 18 h) (Bertolini et al , 1989; Guarini et al , 1990), they nevertheless produce a rapid restoration of tissue perfusion in vital organs (Guarini et al , 1989), of degree and duration sufficient to extend considerably the time within which blood reinfusion can lead to an effective and definitive cure.…”

“…This effect is adrenal‐independent (it is obtained also in adrenalectomized animals, and with melanocortin peptides practically devoid of corticotropic activity) (Bertolini et al , 1986a,c), and is associated with a massive increase in the volume of circulating blood, with consequent restoration of the blood flow (Guarini et al , 1987; 1989), normalization of cardiac output and total peripheral resistances, gradual normalization of arterial and venous pH and base excess (BE), as well as of venous tension of O 2 ( P O 2 ) and CO 2 ( P CO 2 ) and venous oxygen saturation (Hb/O 2 ) and lactate (Bazzani et al , 1992), and with greatly reduced free radical levels in blood (Guarini et al , 1996). Although these peptides do not per se definitively cure haemorrhagic shock (all rats treated with the maximally active dose of 160 μg kg −1 die within 44 ± 18 h) (Bertolini et al , 1989; Guarini et al , 1990), they nevertheless produce a rapid restoration of tissue perfusion in vital organs (Guarini et al , 1989), of degree and duration sufficient to extend considerably the time within which blood reinfusion can lead to an effective and definitive cure. In fact, while all rats reinfused with their own shed blood 15 min after haemorrhage die within 6.6 ±4.4 h, a substantial number of haemorrhage‐shocked rats treated with ACTH‐(1–24) shortly (5–10 min) after bleeding survive indefinitely even if blood reinfusion is performed 30, 60 or 120 min later (Bertolini et al , 1989; Guarini et al , 1990).…”

Influence of ACTH‐(1–24) on free radical levels in the blood of haemorrhage‐shocked rats: direct ex vivo detection by electron spin resonance spectrometry

“…This effect of ACTH-(1-24) is prompt (reaching its maximum 15 min after treatment) and long-lasting (the free radical blood level remains quite stable throughout the 2 h observation period). It parallels the effects of ACTH-(1-24) on arterial pressure and tissue blood flow (Bertolini et al, 1989;Guarini et al, 1989). This effect cannot be attributed to an ACTH-(1-24) radical scavenging activity, as demonstrated by the competition experiment.…”

Melanocortins and the Cholinergic Anti-Inflammatory Pathway

“…Such increase is the consequence of mobilization of the peripherally pooled residual blood from the liver, spleen and other organs. 28,83,85 Subsequent studies using the same experimental model indicated that melanocortins greatly prolong survival and extend the time-limit for effective blood reinfusion (up to 3-4 hours after shock, versus 10-15 min in saline-treated animals) for complete shock reversal. 29 These resuscitating effects have been confirmed in the same animal models of hemorrhagic shock, 86 as well as in hemorrhage-shocked/resuscitated hamsters, 87 in hypovolemic shock induced in rabbits by graded occlusion of the inferior vena cava, 88 in a rat model of splanchnic artery occlusion 34 and in a severe model of prolonged respiratory arrest in rats.…”

“…This procedure causes death in all animals within 30-35 min. 26,27,[81][82][83] Conversely, intravenous injection of melanocortin peptides rapidly induces a dose-dependent restoration of arterial blood pressure and tissue blood flow. Normalization of arterial and venous pH and base excess, as well as of venous tension of O 2 and CO 2 and of venous oxygen saturation and lactate, also gradually occur.…”

Resuscitating effect of melanocortin peptides after prolonged respiratory arrest

“…injection of mela‐nocortin peptides (adrenocorticotrophin (ACTH), α‐melanocyte stimulating hormone (α‐MSH), other ACTH fragments: 1–24, 1–18, 1–17, 1–16, 4–10) in nanomolar amounts, dose‐dependently restores arterial pressure, pulse amplitude and respiratory function, and produces a highly significant prolongation of the survival time (Bertolini et al , 1986a,b,c, 1989; Guarini et al , 1990; Bertolini, 1995). This effect is adrenal‐independent (it is obtained also in adrenalectomized animals, and with melanocortin peptides practically devoid of corticotropic activity) (Bertolini et al , 1986a,c), and is associated with a massive increase in the volume of circulating blood, with consequent restoration of the blood flow (Guarini et al , 1987; 1989), normalization of cardiac output and total peripheral resistances, gradual normalization of arterial and venous pH and base excess (BE), as well as of venous tension of O 2 ( P O 2 ) and CO 2 ( P CO 2 ) and venous oxygen saturation (Hb/O 2 ) and lactate (Bazzani et al , 1992), and with greatly reduced free radical levels in blood (Guarini et al , 1996). Although these peptides do not per se definitively cure haemorrhagic shock (all rats treated with the maximally active dose of 160 μg kg −1 die within 44 ± 18 h) (Bertolini et al , 1989; Guarini et al , 1990), they nevertheless produce a rapid restoration of tissue perfusion in vital organs (Guarini et al , 1989), of degree and duration sufficient to extend considerably the time within which blood reinfusion can lead to an effective and definitive cure.…”

“…This effect is adrenal‐independent (it is obtained also in adrenalectomized animals, and with melanocortin peptides practically devoid of corticotropic activity) (Bertolini et al , 1986a,c), and is associated with a massive increase in the volume of circulating blood, with consequent restoration of the blood flow (Guarini et al , 1987; 1989), normalization of cardiac output and total peripheral resistances, gradual normalization of arterial and venous pH and base excess (BE), as well as of venous tension of O 2 ( P O 2 ) and CO 2 ( P CO 2 ) and venous oxygen saturation (Hb/O 2 ) and lactate (Bazzani et al , 1992), and with greatly reduced free radical levels in blood (Guarini et al , 1996). Although these peptides do not per se definitively cure haemorrhagic shock (all rats treated with the maximally active dose of 160 μg kg −1 die within 44 ± 18 h) (Bertolini et al , 1989; Guarini et al , 1990), they nevertheless produce a rapid restoration of tissue perfusion in vital organs (Guarini et al , 1989), of degree and duration sufficient to extend considerably the time within which blood reinfusion can lead to an effective and definitive cure. In fact, while all rats reinfused with their own shed blood 15 min after haemorrhage die within 6.6 ±4.4 h, a substantial number of haemorrhage‐shocked rats treated with ACTH‐(1–24) shortly (5–10 min) after bleeding survive indefinitely even if blood reinfusion is performed 30, 60 or 120 min later (Bertolini et al , 1989; Guarini et al , 1990).…”

Influence of ACTH‐(1–24) on free radical levels in the blood of haemorrhage‐shocked rats: direct ex vivo detection by electron spin resonance spectrometry

“…This effect of ACTH-(1-24) is prompt (reaching its maximum 15 min after treatment) and long-lasting (the free radical blood level remains quite stable throughout the 2 h observation period). It parallels the effects of ACTH-(1-24) on arterial pressure and tissue blood flow (Bertolini et al, 1989;Guarini et al, 1989). This effect cannot be attributed to an ACTH-(1-24) radical scavenging activity, as demonstrated by the competition experiment.…”

Melanocortins and the Cholinergic Anti-Inflammatory Pathway

“…Such increase is the consequence of mobilization of the peripherally pooled residual blood from the liver, spleen and other organs. 28,83,85 Subsequent studies using the same experimental model indicated that melanocortins greatly prolong survival and extend the time-limit for effective blood reinfusion (up to 3-4 hours after shock, versus 10-15 min in saline-treated animals) for complete shock reversal. 29 These resuscitating effects have been confirmed in the same animal models of hemorrhagic shock, 86 as well as in hemorrhage-shocked/resuscitated hamsters, 87 in hypovolemic shock induced in rabbits by graded occlusion of the inferior vena cava, 88 in a rat model of splanchnic artery occlusion 34 and in a severe model of prolonged respiratory arrest in rats.…”

“…This procedure causes death in all animals within 30-35 min. 26,27,[81][82][83] Conversely, intravenous injection of melanocortin peptides rapidly induces a dose-dependent restoration of arterial blood pressure and tissue blood flow. Normalization of arterial and venous pH and base excess, as well as of venous tension of O 2 and CO 2 and of venous oxygen saturation and lactate, also gradually occur.…”

Resuscitating effect of melanocortin peptides after prolonged respiratory arrest

“…injection of mela‐nocortin peptides (adrenocorticotrophin (ACTH), α‐melanocyte stimulating hormone (α‐MSH), other ACTH fragments: 1–24, 1–18, 1–17, 1–16, 4–10) in nanomolar amounts, dose‐dependently restores arterial pressure, pulse amplitude and respiratory function, and produces a highly significant prolongation of the survival time (Bertolini et al , 1986a,b,c, 1989; Guarini et al , 1990; Bertolini, 1995). This effect is adrenal‐independent (it is obtained also in adrenalectomized animals, and with melanocortin peptides practically devoid of corticotropic activity) (Bertolini et al , 1986a,c), and is associated with a massive increase in the volume of circulating blood, with consequent restoration of the blood flow (Guarini et al , 1987; 1989), normalization of cardiac output and total peripheral resistances, gradual normalization of arterial and venous pH and base excess (BE), as well as of venous tension of O 2 ( P O 2 ) and CO 2 ( P CO 2 ) and venous oxygen saturation (Hb/O 2 ) and lactate (Bazzani et al , 1992), and with greatly reduced free radical levels in blood (Guarini et al , 1996). Although these peptides do not per se definitively cure haemorrhagic shock (all rats treated with the maximally active dose of 160 μg kg −1 die within 44 ± 18 h) (Bertolini et al , 1989; Guarini et al , 1990), they nevertheless produce a rapid restoration of tissue perfusion in vital organs (Guarini et al , 1989), of degree and duration sufficient to extend considerably the time within which blood reinfusion can lead to an effective and definitive cure.…”

“…This effect is adrenal‐independent (it is obtained also in adrenalectomized animals, and with melanocortin peptides practically devoid of corticotropic activity) (Bertolini et al , 1986a,c), and is associated with a massive increase in the volume of circulating blood, with consequent restoration of the blood flow (Guarini et al , 1987; 1989), normalization of cardiac output and total peripheral resistances, gradual normalization of arterial and venous pH and base excess (BE), as well as of venous tension of O 2 ( P O 2 ) and CO 2 ( P CO 2 ) and venous oxygen saturation (Hb/O 2 ) and lactate (Bazzani et al , 1992), and with greatly reduced free radical levels in blood (Guarini et al , 1996). Although these peptides do not per se definitively cure haemorrhagic shock (all rats treated with the maximally active dose of 160 μg kg −1 die within 44 ± 18 h) (Bertolini et al , 1989; Guarini et al , 1990), they nevertheless produce a rapid restoration of tissue perfusion in vital organs (Guarini et al , 1989), of degree and duration sufficient to extend considerably the time within which blood reinfusion can lead to an effective and definitive cure. In fact, while all rats reinfused with their own shed blood 15 min after haemorrhage die within 6.6 ±4.4 h, a substantial number of haemorrhage‐shocked rats treated with ACTH‐(1–24) shortly (5–10 min) after bleeding survive indefinitely even if blood reinfusion is performed 30, 60 or 120 min later (Bertolini et al , 1989; Guarini et al , 1990).…”