• Journal of Chest Surgery
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• v.32 no.7
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• pp.603-612
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• 1999

Background : It has been documented that brief repetitive periods of ischemia and reperfusion (ischemic preconditioning, IP) enhances the recovery of post-ischemic contractile function and reduces infarct size after a longer period of ischemia. Many mechanisms have been proposed to explain this process. Recent studies have suggested that transient increase in the intracellular calcium may have triggered the activation of protein kinase C(PKC); however, there are still many controversies. Accordingly, the author performed the present study to test the hypothesis that preconditioning with high concentration of calcium before sustained subsequent ischemia(calcium preconditioning) mimics IP by PKC activation. Material and Method : The isolated hearts from the New Zealand White rabbits(1.5∼2.0 kg body weight) Method: The isolated hearts from the New Zealand White rabbits(1.5∼2.0 kg body weight) were perfused with Tyrode solution by Langendorff technique. After stabilization of baseline hemodynamics, the hearts were subjected to 45-minute global ischemia followed by a 120-minute reperfusion with IP(IP group, n=13) or without IP(ischemic control, n=10). IP was induced by single episode of 5-minute global ischemia and 10-minute reperfusion. In the Ca2+ preconditioned group, perfusate containing 10(n=10) or 20 mM(n=11) CaCl2 was perfused for 10 minutes after 5-minute ischemia followed by a 45-minute global ischemia and a 120-minute reperfusion. Baseline PKC was measured after 50-minute perfusion without any treatment(n=5). Left ventricular function including developed pressure(LVDP), dP/dt, heart rate, left ventricular end-diastolic pressure(LVEDP) and coronary flow(CF) was measured. Myo car ial cytosolic and membrane PKC activities were measured by 32P-${\gamma}$-ATP incorporation into PKC-specific pepetide. The infarct size was determined using the TTC (tetrazolium salt) staining and planimetry. Data were analyzed using one-way analysis of variance(ANOVA) variance(ANOVA) and Tukey's post-hoc test. Result: IP increased the functional recovery including LVDP, dP/dt and CF(p<0.05) and lowered the ascending range of LVEDP(p<0.05); it also reduced the infarct size from 38% to 20%(p<0.05). In both of the Ca2+ preconditioned group, functional recovery was not significantly different in comparison with the ischemic control, however, the infarct size was reduced to 19∼23%(p<0.05). In comparison with the baseline(7.31 0.31 nmol/g tissue), the activities of the cytosolic PKC tended to decrease in both the IP and Ca2+ preconditioned groups, particularly in the 10 mM Ca2+ preconditioned group(4.19 0.39 nmol/g tissue, p<0.01); the activity of membrane PKC was significantly increased in both IP and 10 mM Ca2+ preconditioned group (p<0.05; 1.84 0.21, 4.00 0.14, and 4.02 0.70 nmol/g tissue in the baseline, IP, and 10 mM Ca2+ preconditioned group, respectively). However, the activity of both PKC fractions were not significantly different between the baseline and the ischemic control. Conclusion: These results indicate that in isolated Langendorff-perfused rabbit heart model, calcium preconditioning with high concentration of calcium does not improve post-ischemic functional recovery. However, it does have an effect of limiting(reducing) the infart size by ischemic preconditioning, and this cardioprotective effect, at least in part, may have resulted from the activation of PKC by calcium which acts as a messenger(or trigger) to activate membrane PKC.

• The Korean Journal of Air & Space Law and Policy
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• v.28 no.2
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• pp.223-258
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• 2013

1967 Outer Space Treaty(Treaty on Principles Governing the Activities of States in the Exploration and Use of Outer Space, including the Moon and Other Celestial Bodies; OST) is a treaty that forms the basis of international space law. OST is based on the 1963 Declaration of Legal Principles Governing the Activities of States in the Exploration and Use of Outer Space announced by UNGA resolution. As of May 2013, 102 countries are states parties to OST, while another 27 have signed the treaty but have not completed ratification. OST explicitly claimed that the Moon and Other Celestial Bodies are the province of all mankind. Art. II of OST states that "outer space, including the Moon and other celestial bodies, is not subject to national appropriation by claim of sovereignty, by means of use or occupation, or by any other means", thereby establishing res extra commercium in outer space like high seas. However 1979 Moon Agreement stipulates that "the moon and its natural resources are the Common Heritage of Mankind(CHM)." Because of the number of the parties to the Moon Agreement(13 parties) it does not affect OST. OST also established its specific treaties as a complementary means such as 1968 Rescue Agreement, 1972 Liability Convention, 1975 Registration Convention. OST bars states party to the treaty from placing nuclear weapons or any other weapons of mass destruction in orbit of Earth, installing them on the Moon or any other celestial body, or to otherwise station them in outer space. It exclusively limits the use of the Moon and other celestial bodies to peaceful purposes and expressly prohibits their use for testing weapons of any kind, conducting military maneuvers, or establishing military bases, installations, and fortifications. However OST does not prohibit the placement of conventional weapons in orbit. China and Russia submitted Draft Treaty on the Prevention of the Placement of Weapon in Outer Space and of the Threat or Use of Force against Outer Space Objects(PPWT) on the Conference on Disarmament in 2008. USA disregarded PPWT on the ground that there are no arms race in outer space. OST does not have some articles in relation to current problems such as space debris, mechanisms of the settlement of dispute arising from state activities in outer space in specific way. COPUOS established "UN Space Debris Mitigation Guidelines" based on "IADC Space Debris Mitigation Guidelines" and ILA proposed "International Instrument on the Protection of the Environment from Damage Caused by Space Debris" for space debris problems and Permanent Court of Arbitration(PCA) established "Optional Rules for Arbitration of Disputes Relating to Outer Space Activities" and ILA proposed "1998 Taipei Draft Convention on the Settlement of Space Law Dispute" for the settlement of dispute problems. Although OST has shortcomings in some articles, it is very meaningful in international law in considering the establishment of basic principles governing the activities of States in the exploration and use of outer space, including the Moon and Other Celestial Bodies. OST established the principles governing the activities of states in the exploration and use of outer space as customary law and jus cogens in international law as follows; the exploration and use of outer space shall be carried out for the benefit and in the interests of all countries and shall be the province of all mankind; outer space shall be free for exploration and use by all States; outer space is not subject to national appropriation by claim of sovereignty, by means of use or occupation, or by any other means. The principles of global public interest in outer space imposes international obligations erga omnes applicable to all States. This principles find significant support in legal norms dealing with following points: space activities as the "province of all mankind"; obligation to cooperate; astronauts as envoys of mankind; avoidance of harmful contamination; space activities by States, private entities and intergovernmental organisations; absolute liability for damage cauesd by certain space objects; prohibition of weapons in space and militarization of the celestial bodies; duty of openness and transparency; universal application of the international space regime.