Impact of Anesthetics on Cardioprotection Induced by Pharmacological Preconditioning

Abstract

Anesthetics, especially propofol, are discussed to influence ischemic preconditioning. We investigated whether cardioprotection by milrinone or levosimendan is influenced by the clinically used anesthetics propofol, sevoflurane or dexmedetomidine. Hearts of male Wistar rats were randomised, placed on a Langendorff system and perfused with Krebs–Henseleit buffer (KHB) at a constant pressure of 80 mmHg. All hearts underwent 33 min of global ischemia and 60 min of reperfusion. Three different anesthetic regimens were conducted throughout the experiments: propofol (11 μM), sevoflurane (2.5 Vol%) and dexmedetomidine (1.5 nM). Under each anesthetic regimen, pharmacological preconditioning was induced by administration of milrinone (1 μM) or levosimendan (0.3 μM) 10 min before ischemia. Infarct size was determined by TTC staining. Infarct sizes in control groups were comparable (KHB-Con: 53 ± 9%, Prop-Con: 56 ± 9%, Sevo-Con: 56 ± 8%, Dex-Con: 53 ± 9%; ns). Propofol completely abolished preconditioning by milrinone and levosimendan (Prop-Mil: 52 ± 8%, Prop-Lev: 52 ± 8%; ns versus Prop-Con), while sevoflurane did not (Sevo-Mil: 31 ± 9%, Sevo-Lev: 33 ± 7%; p < 0.05 versus Sevo-Con). Under dexmedetomidine, results were inconsistent; levosimendan induced infarct size reduction (Dex-Lev: 36 ± 6%; p < 0.05 versus Dex-Con) but not milrinone (Dex-Mil: 51 ± 8%; ns versus Dex-Con). The choice of the anesthetic regimen has an impact on infarct size reduction by pharmacological preconditioning.

Pharmacological Conditioning of the Heart: An Update on Experimental Developments and Clinical Implications

“…Comparable with these counteracting effects of propofol on RIPC, pharmacological-induced cardioprotection is also mitigated by propofol. Protective effects against myocardial I/R injury by preconditioning with phosphodiesterase inhibitors such as milrinone or levosimendan are fully abolished by propofol perfusion in an isolated rat heart I/R [ 69 ]. Similar results were observed in a working heart model by Lucchinetti et al investigating postconditioning with Intralipid (ILPostC) [ 70 ].…”

“…Noteworthy—and relevant for a possible translation into the clinical setting—, preconditioning effects of milrinone seem to depend on the anesthetic regimen: simultaneous perfusion with propofol or dexmedetomidine results in complete abrogation of cardioprotective properties by milirinone in isolated rat hearts [ 69 ]. This phenomenon was not found for simultaneous administration of sevoflurane.…”

“…Further studies did show that protection against I/R injury by levosimendan is meditated by mBK Ca , channels [ 124 , 125 ]. Interestingly, this agent forfeits its cardioprotective properties under simultaneous administration of propofol, but not under sevoflurane or dexmedetomidine anesthesia [ 69 ].…”

Vom Verständnis zur Therapie der perioperativen Inflammation

“…Zahlreiche Tiermodelle konnten zeigen, dass Anästhetika einen präkonditionierenden (protektiven) Effekt auf das Herz und andere Organe gegenüber einer Ischämie haben. Es sind zahlreiche Mechanismen und Signalwege beschrieben worden, die diesen Effekt erklären [4]. Leider haben jedoch klinische Studien beim Menschen diese Wirkung bisher in dieser Ausprägung nicht nachvollziehen können.…”

Propofol Requirement in Patients with Growth Hormone-Secreting Pituitary Tumors Undergoing Transsphenoidal Surgery

“…Propofol is known to be better than inhalation agents for reducing the incidence of agitation and delirium after general anesthesia and is widely used in transsphenoidal pituitary surgery. Propofol exerts a sedative effect by activating the receptor for gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the central nervous system [3,4,5]. The pharmacokinetics of propofol can be altered by various factors, including age, sex, weight, concomitant medications, and underlying diseases, so it is important to tailor the dose to the individual patient’s requirements [6].…”