Effect of type 2 diabetes, surgical incision, and volatile anesthesia on hemodynamics in the rat

Figures

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  Figure 1. Experimental design. The overall experimental design (A). Animals were gentled for 7 days prior to implantation surgery of a radiotelemeter and vascular access port (VAP), followed by 10‐day postsurgical recovery during which VAP patency was maintained by biweekly flush. Here, after the 10‐day experimental period was started, consisting of three measurement sessions: under conscious conditions, isoflurane anesthesia, and isoflurane anesthesia including a sham surgery. To prevent adrenergic receptor desensitization at least a 2‐day period was maintained between sessions. A measurement session of the experimental protocol (B). An equilibration period of 20 min followed insertion of the needle into the VAP. After 30 min, or 10 min after surgical incision, phenylephrine (PE, α‐adrenoceptor agonist, 10 μg·kg−1) and sodium nitroprusside (SNP, nitric oxide donor, 10 μg·kg−1) were injected 8 min apart in random order, with the VAP flushed between each administration. At the end, because of their longer lasting effects, the response to atropine (muscarinic receptor blocker, 1 mg·kg−1) or nadolol (nonselective β‐adrenoceptor blocker, 4 mg·kg−1) was tested.

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  Figure 2. Baseline hemodynamics. Under conscious (Con) conditions mean arterial pressure (MAP) was not different (A) and heart rate (HR) was lower (D) in diabetic (DM) compared to nondiabetic (ND) animals. MAP was reduced by isoflurane anesthesia (Ana), along with HR in both ND and DM animals. The decrease in MAP to anesthesia (B) was similar, but the decrease in HR (E) was less in DM rats. Surgical incision (Surg) increased MAP (C), which was slightly less in DM animals, but surgical incision did not change HR (F). Detailed hemodynamic effects of surgical incision showed that MAP (G) rose under isoflurane anesthesia with increasing depth of surgical incision from skin through the muscle layers into the abdomen, with no change in HR (H). The increase in MAP was slightly less in the DM compared to ND animals (A–F) n = 11–14 per group, (G–H) n = 6 per group; *P < 0.05 vs. Con, # P < 0.05 vs. Ana, † P < 0.05 vs. ND.

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  Figure 3. Parasympathetic system. Parasympathetic (PS) blockade with atropine 1 mg·kg−1 immediately, within seconds, tended to reduce mean arterial pressure (MAP) (A), which was not sustained after 10 min (B). Surgical incision (Surg), but not anesthesia (Ane), significantly exacerbated the acute vasodilation in response to PS blockade in the nondiabetic (ND) animals. This was accompanied by a marked acute (C) and sustained (D) increase in HR in the conscious (Con) animals, which was abolished under anesthesia with no additional effect of surgical incision. No differences were observed between ND and diabetic (DM) animals. n = 5–8, *P < 0.05 vs. Con.

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  Figure 4. β‐adrenergic system. Blockade of the sympathetic system (SS) with nadolol 4 mg·kg−1 immediately (within seconds) tended to reduce mean arterial pressure (MAP) (A), although this effect did not persist 10 min after administration (B). Surgical incision (Surg), but not anesthesia (Ane), significantly exacerbated the acute vasodilation in response to SS blockade in nondiabetic (ND) animals. SS blockade with nadolol induced an acute (C) and sustained (D) decrease in heart rate (HR) in the conscious (Con) animals, which was not significantly altered by anesthesia or surgical incision. No differences were observed between ND and diabetic (DM) animals. n = 5–6, *P < 0.05 vs. Con.

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  Figure 5. Baroreflex responses. Phenylephrine (10 μg·kg−1) increased mean arterial pressure (MAP) (A) and lowered heart rate (HR) (B) in conscious (Con) conditions. Anesthesia (Ane) reduced the peripheral vasoconstriction and disrupted the central sympathetic withdrawal baroreflex, with no additional effect of surgical incision (Surg). Sodium nitroprusside (10 μg·kg−1) decreased MAP (C) and increased HR (D), whereas anesthesia reduced the peripheral vasodilatation and disrupted the central sympathetic activation baroreflex with no additional effect of surgical incision. No differences were observed between nondiabetic (ND) and diabetic (DM) animals for any of the responses. n = 11–14, *P < 0.05 vs. Con.