Deep Hypothermic Circulatory Arrest: Real-Life Suspended Animation

Deep hypothermic circulatory arrest (DHCA) is a cerebral protection technique that was developed in the 1950s and popularized in the 1970s. It has become one of the three most common cerebral protection techniques currently used in aortic arch surgeries, with the other two being antegrade cerebral perfusion (ACP) and retrograde cerebral perfusion (RCP). At our institution, DHCA has been the cerebral protection technique of choice for over a quarter century. Our clinical experience with DHCA has been very positive, and our clinical studies have shown DHCA to have outcomes equal to (and sometimes better than) those of ACP and RCP, and DHCA to be very effective at preserving neurocognitive function. Other institutions, however, prefer ACP or RCP to DHCA. Each technique has its own set of pros and cons, and the question regarding which technique is the superior method for cerebral protection is hotly debated.     

Aortic Delamination—A Possible Precursor of Impending Catastrophe

Aortic diameter is a powerful predictor of adverse aortic events, such as aortic rupture or dissection, forming the basis of prophylactic surgical repair criteria. Limited evidence is available regarding the association of aortic wall thickness (AWT) with these adverse aortic events. We present the case and surgical video of a 73-year-old man with chest pain and an increased AWT, who underwent ascending aortic repair and deep hemiarch placement under deep hypothermic circulatory arrest. Surgical pathology demonstrated evidence of aortic delamination and medial separation, indicative of an impending dissection. The patient recovered uneventfully, and his chest pain ultimately resolved after open repair. In this patient, increased AWT was felt to be the precursor to a potential aortic catastrophe.     

Clinicopathological features of megaloblastic anaemia in Hong Kong: a study of 84 Chinese patients

Megaloblastic anaemia is uncommon in Hong Kong. Eighty-four consecutive Chinese patients with megaloblastic anaemia were studied. There were 48 males and 36 females, with a median age at presentation of 67 years. Vitamin B12 deficiency was found in all cases, with none of the patients showing folate deficiency. The frequency of pernicious anaemia in our patients was higher than in other south-east Asian series but comparable with western ones. When compared with patients in the West, our cases showed the following main differences: virtual absence of folate deficiency, even in alcoholics; absence of associated gastric malignancies; and a high frequency of tuberculosis.     

Potentiation by 2,2'-pyridylisatogen tosylate of ATP-responses at a recombinant P2Y1 purinoceptor.

1. 2,2''-Pyridylisatogen tosylate (PIT) has been reported to be an irreversible antagonist of responses to adenosine 5''-triphosphate (ATP) at metabotropic purinoceptors (of the P2Y family) in some smooth muscles. When a recombinant P2Y1 purinoceptor (derived from chick brain) is expressed in Xenopus oocytes, ATP and 2-methylthioATP (2-MeSATP) evoke calcium-activated chloride currents (ICl,Ca) in a concentration-dependent manner. The effects of PIT on these agonist responses were examined at this cloned P2Y purinoceptor. 2. PIT (0.1-100 microM) failed to stimulate P2Y1 purinoceptors directly but, over a narrow concentration range (0.1-3 microM), caused a time-dependent potentiation (2-5 fold) of responses to ATP. The potentiation of ATP-responses by PIT was not caused by inhibition of oocyte ecto-ATPase. At high concentrations (3-100 microM), PIT irreversibly inhibited responses to ATP with a IC50 value of 13 +/- 9 microM (pKB = 4.88 +/- 0.22; n = 3). PIT failed to potentiate inward currents evoked by 2-MeSATP and only inhibited the responses to this agonist in an irreversible manner. 3. Known P2 purinoceptor antagonists were tested for their ability to potentiate ATP-responses at the chick P2Y1 purinoceptor. Suramin (IC50 = 230 +/- 80 nM; n = 5) and Reactive blue-2 (IC50 = 580 +/- 130 nM; n = 6) reversibly inhibited but did not potentiate ATP-responses. Coomassie brilliant blue-G (0.1-3 microM) potentiated ATP-responses in three experiments, while higher concentrations (3-100 microM) irreversibly inhibited ATP-responses. The results indicated that potentiation and receptor antagonism were dissociable and not a feature common to all known P2 purinoceptor antagonists. 4. In radioligand binding assays, PIT showed a low affinity (pKi < 5) for a range of membrane receptors, including: alpha 1, alpha 2-adrenoceptors, 5-HT1A, 5-HT1B, 5-HT2, 5-HT3, D1, D2, muscarinic, central benzodiazepine, H1, mu-opioid, dihydropyridine and batrachotoxin receptors. PIT showed some affinity (pKi = 5.3) for an adenosine (A1) receptor. 5. In guinea-pig isolated taenia caeci, PIT (12.5-50 microM) irreversibly antagonized relaxations to ATP (3-1000 microM); PIT also directly relaxed the smooth muscle and histamine was used to restore tone. Relaxations to nicotine (10-100 microM), evoked by stimulating intrinsic NANC nerves of taenia caeci preparations in the presence of hyoscine (0.3 microM) and guanethidine (17 microM), were not affected by PIT (50 microM, for 25-60 min). 6. These experiments indicate that PIT causes an irreversible antagonism of ATP receptors but, for recombinant chick P2Y1 purinoceptors, this effect is preceded by potentiation of ATP agonism. The initial potentiation by PIT (and by Coomassie brilliant blue-G) of ATP-responses raises the possibility of designing a new class of modulatory drugs to enhance purinergic transmission at metabotropic purinoceptors.     

The activation of P1- and P2-purinoceptors in the guinea-pig left atrium by diadenosine polyphosphates.

1. The effects of P1, P2-di(adenosine) pyrophosphate (AP2A), P1, P3-di(adenosine) triphosphate (AP3A), P1,P4-di(adenosine) tetraphosphate (AP4A), P1,P5-di(adenosine) pentaphosphate (AP5A), ATP, alpha, beta-methylene ADP and 2-chloroadenosine (2-ClAd) were examined in the guinea-pig driven left atrium. 2. All these purine compounds except alpha, beta-methylene ADP produced a negative inotropic response with a rank order of potency of: 2-ClAd > > AP2A > or = ATP > or = AP4A = AP3A = AP5A. The EC50 value for 2-ClAd was approximately 1 microM, while those for the remaining compounds were in the range 10 microM-100 microM, alpha, beta-Methylene ADP (10-300 microM), a selective P2Y-purinoceptor agonist, produced a small positive inotropism. 3. The P1-purinoceptor antagonist, 8-para-sulphophenyltheophylline (8-pSPT, 20 microM) caused a right-ward shift in the concentration-response curves for 2-ClAd, ATP and AP2A, but converted the responses of AP3A, AP4A, and AP5A into positive inotropisms. 4. The non-selective P2-purinoceptor antagonist, suramin (300 microM), had no significant effect on the concentration-response curves for 2-ClAd, ATP or AP2A, but significantly antagonized inhibitory responses to AP3A, AP4A and AP5A, and excitatory responses to alpha, beta-methylene ADP. 5. In the presence of 8-pSPT (20 microM), suramin (300 microM) abolished the positive inotropic responses evoked by the dinucleotides. 6. ATP was degraded far more rapidly than any of the dinucleotides, and AP3A was the least stable of the diadenosine compounds. The relative order of stability was AP2A > AP4A = AP5A > AP3A > > ATP. Suramin (300 microM) reduced the rate of degradation of ATP and AP3A by approximately 30%. Suramin had no significant effect on the degradation of AP2A, AP4A or AP5A. 7. It is concluded that the diadenosine polyphosphates cause negative inotropic responses via P1-purinoceptors and a hitherto undefined suramin-sensitive P2-purinoceptor, and that they appear to have positive inotropic effects mediated via another suramin-sensitive P2-purinoceptor.     

Potentiation of uterine effects of prostaglandin F2{alpha} by adenosine 5'-triphosphate

OBJECTIVE: To investigate the interaction of exogenous adenosine 5'-triphosphate (ATP), a P2 receptor agonist, with prostaglandin F(2alpha) (PGF(2alpha)) on pregnant women in labor as well as on isolated human pregnant uterus preparations. METHODS: For an in vitro study, myometrial samples were obtained from 27 women undergoing elective cesarean delivery at term. Concentration-response relationships for ATP (10(-8) -3 x 10(-4) mol/L), PGF(2alpha) (10(-9) -10(-5) mol/L), and their combination were obtained by using routine pharmacological organ bath technique. An in vivo study was performed with 34 pregnant women with dysfunctional abnormalities of the active stage of labor who were randomly allocated into 2 study groups. The women in the control group (18 patients) received intravenous prostaglandin F(2alpha) at an initial rate of 7.5 mug/min, whereas the women in the ATP group (16 patients) received prostaglandin F(2alpha) concomitantly with ATP (0.45 nmol/min, intravenously). RESULTS: Adenosine 5'-triphosphate at concentrations of 10(-6) -3 x 10(-4) mol/L and PGF(2alpha) at concentrations of 10(-8) -10(-5) mol/L caused concentration-dependent contractions of isolated smooth muscle preparations of the human pregnant uterus. At concentrations of 10(-6) mol/L and below, ATP had no effects on mechanical activity of the isolated uterus, but at concentrations of 10(-7) mol/L and 10(-6) mol/L, it significantly potentiated the contractile responses of the uterus induced by PGF(2alpha) (P < .05, 2-way analysis of variance). Patients receiving intravenous infusion of ATP as a supplement to PGF(2alpha) treatment, compared with those without ATP, had a significantly shorter interval from the start of the treatment to full cervical dilatation (3.31 +/- 1.49 hours and 4.67 +/- 1.11 hours in ATP and control groups, respectively; P = .014, Wilcoxon Mann-Whitney test). The total dose of prostaglandin received was significantly lower in the ATP group than that of controls (1,489.8 +/- 699.9 mug and 3,394.2 +/- 1,951.9 mug, respectively; P = .003, Wilcoxon Mann-Whitney test). No side effects of ATP treatment were observed during or after infusion. CONCLUSION: Adenosine 5'-triphosphate potentiates effects of PGF(2alpha) on pregnant human uterus in vitro and in vivo and thus could be a useful supplemental drug to increase uterine contractility at labor.     

Stimulation of Vagus Nerve Modifies Negative Chronotropic and Hypotensive Effects of Adenosine

The effects of electrical stimulation of the vagus nerve on the negative chronotropic and hypotensive effects of adenosine were studied on adult rats. Intravenous injection of adenosine to control rats significantly reduced the heart rate and induced a transient blood pressure drop followed its increase. Preliminary electrical stimulation of the right vagus nerve reduced the magnitude and duration of adenosine-induced bradycardia and changed the dynamics of adenosine-induced arterial pressure perturbations.